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Information on EC 2.7.11.25 - mitogen-activated protein kinase kinase kinase
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2.7.11.25 mitogen-activated protein kinase kinase kinaseIUBMB Comments
This enzyme phosphorylates and activates its downstream protein kinase, EC 2.7.12.2, mitogen-activated protein kinase kinase (MAPKK) but requires MAPKKKK for activation. Some members of this family can be activated by p21-activated kinases (PAK/STE20) or Ras. While c-Raf and c-Mos activate the classical MAPK/ERK pathway, MEKK1 and MEKK2 preferentially activate the c-Jun N-terminal protein kinase(JNK)/stress-activated protein kinase (SAPK) pathway . Mitogen-activated protein kinase (MAPK) signal transduction pathways are among the most widespread mechanisms of cellular regulation. Mammalian MAPK pathways can be recruited by a wide variety of stimuli including hormones (e.g. insulin and growth hormone), mitogens (e.g. epidermal growth factor and platelet-derived growth factor), vasoactive peptides (e.g. angiotensin-II and endothelin), inflammatory cytokines of the tumour necrosis factor (TNF) family and environmental stresses such as osmotic shock, ionizing radiation and ischaemic injury.
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Word Map
- 2.7.11.25
- mapks
- c-jun
- ask1
- necrosis
- melanoma
- proto-oncogene
-
necroptosis
-
domain-like
- mlkl
- tnf
- raf-1
-
receptor-interacting
- oocyte
- nf-kappab
- c-myc
- ripk1
-
dominant-negative
-
meiotic
- sorafenib
- pheromone
- cyclins
-
pseudokinase
- vemurafenib
- ikappab
- pik3ca
- traf2
- n-ras
-
receptor-associated
-
serine-threonine
- analysis
- dabrafenib
- erk5
- mek-1
-
p21-activated
-
kirsten
-
ras-dependent
- p38alpha
-
jnk-dependent
-
kinase-inactive
-
mixed-lineage
-
necrostatin-1s
-
mek-erk
- medicine
-
jnk-mediated
-
braf-mutant
- ikkalpha
-
kinase-dead
-
multikinase
-
ras-induced
- trametinib
-
brafv600e
- ikkbeta
The enzyme appears in viruses and cellular organisms
Reaction Schemes
+
a [protein]-(L-serine/L-threonine)
=
+
a [protein]-(L-serine/L-threonine) phosphate
Synonyms
b-raf, c-raf, mekk1, c-mos, apoptosis signal-regulating kinase 1, mixed lineage kinase, ste11, mekk3, map3k1, mapkkk, 
more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
apoptosis signal-regulating kinase 1
apoptosis signal-regulating kinase 2
ASK1
ASK2
At4g08480
At4g08500
B-Raf
BcOs4
c-mos
C-Raf
COT
D-MEKK1
DLK
Dual leucine zipper bearing kinase
EC 2.7.1.37
-
-
formerly, part transferred
-
fertilization-related kinase 1
fertilization-related kinase 2
Frk1
Frk2
GCKR
germinal center kinase-related enzyme
HsNIK
-
-
-
-
Leucine-zipper protein kinase
-
-
-
-
MAP 3-kinase
MAP kinase kinase kinase
MAP kinase kinase kinase 1
MAP kinase kinase kinase 2
MAP kinase kinase kinase 3
MAP/ERK kinase kinase 1
MAP3K
MAP3K1
MAP3Ka
MAPK kinase kinase
MAPK-upstream kinase
-
-
-
-
MAPK/ERKkinase kinase 3
MAPKKK
MAPKKK6
MAPKKKalpha
MEK kinase 1
MEKK
MEKK1
MEKK2
MEKK3
MEKK4
mitogen-activated protein kinase kinase kinase
mitogen-activated protein kinase kinase kinase 1
mitogen-activated protein kinase kinase kinase 20
mitogen-activated protein kinase kinase kinase 4
mitogen-activated protein kinase kinase kinase kinase
mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase 1
-
mitogen-activated protein kinase/extracellular-regulated kinase kinase kinase-3
-
-
mitogen-activated protein kinase/extracellular-signal-regulated kinase kinase kinase 1
-
-
MKKK
MLK
MLK2
MLK3
MLK4
Mos
MTK1
MUK
NF-kappa beta-inducing kinase
-
-
-
-
Raf10
Raf11
Serine/threonine protein kinase NIK
-
-
-
-
summ1
suppressor of mkk1 mkk2 1
TAK1
TPL-2
transforming growth factor beta-activated kinase 1
Wak1
Wik1
Win1
Wis4
ZPK
additional information
c-mos
-
-
-
-
DLK
-
-
-
-
Dual leucine zipper bearing kinase
-
-
-
-
MEKK1
-
-
MUK
-
-
-
-
ZPK
-
-
-
-
additional information
-
MEKK2 and MEKK3 belong to the MEKK/Ste11 subfamily of the MAP3K family of enzymes
additional information
-
MAP kinase cascade is homologous to the Saccharomyces cerevisiae Slt2p pathway
additional information
MAPKKKalpha belongs to the A2 subgroup of the MEKK enzyme family
additional information
MAPKKKalpha belongs to the A2 subgroup of the MEKK enzyme family
additional information
-
the enzyme belongs to the MLK family of mitogen activated protein kinase kinase kinases
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ATP + a [protein]-(L-serine/L-threonine) = ADP + a [protein]-(L-serine/L-threonine) phosphate
ATP + a [protein]-(L-serine/L-threonine) = ADP + a [protein]-(L-serine/L-threonine) phosphate
-
-
-
-
ATP + a [protein]-(L-serine/L-threonine) = ADP + a [protein]-(L-serine/L-threonine) phosphate
Lys391 is the catalytic residue
-
ATP + a [protein]-(L-serine/L-threonine) = ADP + a [protein]-(L-serine/L-threonine) phosphate
mechanism of ASK1
-
ATP + a [protein]-(L-serine/L-threonine) = ADP + a [protein]-(L-serine/L-threonine) phosphate
molecular mechanism of MEKK2 and MEKK3
-
ATP + a [protein]-(L-serine/L-threonine) = ADP + a [protein]-(L-serine/L-threonine) phosphate
structure-function relationship of MAPKKKs and MAPKKs, K1371 is the catalytic residue of MTK1, MTK1, TAK1, and MEKK1 also possess lysine as catalytic residues
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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SYSTEMATIC NAME
IUBMB Comments
ATP:protein phosphotransferase (MAPKKKK-activated)
This enzyme phosphorylates and activates its downstream protein kinase, EC 2.7.12.2, mitogen-activated protein kinase kinase (MAPKK) but requires MAPKKKK for activation. Some members of this family can be activated by p21-activated kinases (PAK/STE20) or Ras. While c-Raf and c-Mos activate the classical MAPK/ERK pathway, MEKK1 and MEKK2 preferentially activate the c-Jun N-terminal protein kinase(JNK)/stress-activated protein kinase (SAPK) pathway [2]. Mitogen-activated protein kinase (MAPK) signal transduction pathways are among the most widespread mechanisms of cellular regulation. Mammalian MAPK pathways can be recruited by a wide variety of stimuli including hormones (e.g. insulin and growth hormone), mitogens (e.g. epidermal growth factor and platelet-derived growth factor), vasoactive peptides (e.g. angiotensin-II and endothelin), inflammatory cytokines of the tumour necrosis factor (TNF) family and environmental stresses such as osmotic shock, ionizing radiation and ischaemic injury.
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CAS REGISTRY NUMBER
COMMENTARY
146702-84-3
-
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + c-Jun
ADP + phosphorylated c-Jun
MAP3K1 phosphorylates and activates a JNK-c-Jun module
-
-
?
ATP + F-kappaB luciferase
ADP + phosphorylated F-kappaB luciferase
-
Ser526 and Thr530 are required for MEKK3-dependent activity
-
-
?
ATP + GLI1
ADP + phosphorylated GLI1
-
mitogen-activated kinase kinase kinase 1 phosphorylates the C-terminal region of GLI1
-
-
?
ATP + SEK
ADP + phosphorylated SEK
-
recombinant GST-tagged inactive KR-mutant SEK, i.e. SAPK/ERK or stress-activated protein kinase/extracellular-signal-regulated kinase, substrate
-
-
?
ATP + SMRT
ADP + phosphorylated SMRT
-
SMRT is regulated by MAPKKK cascades that induce its release from its receptor partners, its export from nucleus to cytoplasm, and derepression of target gene expression. SMRTalpha, SMRTtau, and SMRTsp2 splice variants are released from their nuclear receptor partners in response to MAPKKK activation, the SMRTsp18 variant, which resembles N-CoR in its overall molecular architecture, is relatively refractory to this kinase-induced release
-
-
?
ATP + WRKY53
ADP + phosphorylated WRKY53
-
phosphorylation increases DNA-binding activity of WRKY53
-
-
?
BAD + ATP
BAD-phosphate + ADP
-
activation of the proapoptotic protein BAD
-
-
?
MAP2K + ATP
MAP2K-phosphate + ADP
-
involved in reducing c-jun N-terminal kinase (JNK, MAPK8) activation and protecting the mice from nickel-induced acute lung injury
-
-
?
MEK-1 + ATP
phosphorylated MEK-1 + ADP
-
essential step of the MAP-kinase cascade, activation of MEK-1 which is a MAPKK, essential role in vegetative hyphal growth, conidiation and protoperithecial development, as well as a more limited involvement in maintenance of cell wall integrity, not essential for the resistance to osmotic stress, negatively regulates tyrosinase expression
-
-
?
ATP + ASK1
ADP + phosphorylated ASK1
ASK2 activates ASK1 by direct phosphorylation
-
-
?
ATP + ASK1
ADP + phosphorylated ASK1
ASK2 activates ASK1 by direct phosphorylation
-
-
?
ATP + Atf1
ADP + phosphorylated Atf1
MAPK kinase Atf1 activation
-
-
?
ATP + Atf1
ADP + phosphorylated Atf1
MAPK kinase Atf1 activation
-
-
?
ATP + BcSak1
ADP + phosphorylated BcSak1
BcSak1 is a putative downstream component of BcOs4
-
-
?
ATP + BcSak1
ADP + phosphorylated BcSak1
BcSak1 is a putative downstream component of BcOs4
-
-
?
ATP + ERK
ADP + phosphorylated ERK
-
i.e. extracellular signal-regulated kinase
-
-
?
ATP + ERK
ADP + phosphorylated ERK
-
PI3K/PKC/Raf-1-independent activation of the MEK/ERK signaling pathway
-
-
?
ATP + ERK
ADP + phosphorylated ERK
-
PI3K/PKC/Raf-1-independent activation of the MEK/ERK signaling pathway
-
-
?
ATP + ERK
ADP + phosphorylated ERK
-
MEKK3-dependent activation correlates with a requirement for serine at position 526
-
-
?
ATP + ERK5
ADP + phosphorylated ERK5
-
substrate of MEKK2 and MEKK3, activation of the ERK-dependent signaling pathway
-
-
?
ATP + ERK5
ADP + phosphorylated ERK5
-
substrate of MEKK2 and MEKK3, no substrate of TAO2-1
-
-
?
ATP + GSK3beta
ADP + phosphorylated GSK3beta
-
regulates phosphorylation at serine 9
-
-
?
ATP + GSK3beta
ADP + phosphorylated GSK3beta
-
regulates phosphorylation at serine 9
-
-
?
ATP + GSK3beta
ADP + phosphorylated GSK3beta
-
regulates phosphorylation at serine 9
-
-
?
ATP + JNK
ADP + phosphorylated JNK
activated by ASK2 in complex with ASK1
-
-
?
ATP + JNK
ADP + phosphorylated JNK
-
required for Wnt-mediated JNK activation in B cells
-
-
?
ATP + JNK
ADP + phosphorylated JNK
-
required for Wnt-mediated JNK activation in B cells
-
-
?
ATP + JNK
ADP + phosphorylated JNK
-
required for Wnt-mediated JNK activation in B cells
-
-
?
ATP + JNK
ADP + phosphorylated JNK
-
MEKK3-dependent activation correlates with a requirement for serine at position 526
-
-
?
ATP + MEK
ADP + phosphorylated MEK
-
PI3K/PKC/Raf-1-independent activation of the MEK/ERK signaling pathway
-
-
?
ATP + MEK
ADP + phosphorylated MEK
-
substrate is a MAPKK, usage of inactivated GST-tagged mutant MEK
-
-
?
ATP + MEK
ADP + phosphorylated MEK
-
PI3K/PKC/Raf-1-independent activation of the MEK/ERK signaling pathway
-
-
?
ATP + MEK1
ADP + phosphorylated MEK1
activation by MEKK3 of MAPK signaling pathways
-
-
?
ATP + MEK1
ADP + phosphorylated MEK1
-
MEK1 activates the ERK2 signaling pathway
-
-
?
ATP + MEK1
ADP + phosphorylated MEK1
-
Ras-induced activation of the MAPK signaling cascade
-
-
?
ATP + MEK1
ADP + phosphorylated MEK1
-
the substrate of B-Raf and C-Raf is a MAPKK, no substrate of Mos, recombinant GST-MEK1 substrate
-
-
?
ATP + MEK2
ADP + phosphorylated MEK2
activation by MEKK3 of MAPK signaling pathways
-
-
?
ATP + MEK5
ADP + phosphorylated MEK5
-
MEKK3 and MEK5 form a heterodimer via PB1-PB1 domain interaction, residues Lys 7 and Arg 5 play important roles in the interaction with MEK5 PB1, MEKK3 PB1 binds MEK5 PB1 tightly with a Kd of about 10-8 M
-
-
?
ATP + MKK
ADP + phosphorylated MKK
-
induction of the JNK pathway activation
-
-
?
ATP + MKK1
ADP + phosphorylated MKK1
-
MKK1 activates the ERK2 signaling pathway
-
-
?
ATP + MKK1
ADP + phosphorylated MKK1
-
a MAPKK, recombinant GST-tagged MKK1
-
-
?
ATP + MKK3
ADP + phosphorylated MKK3
the isoform MKKK20 C-terminal region interacts with MKK3
-
-
?
ATP + MKK3
ADP + phosphorylated MKK3
substrate Brassica napus MAPK kinase 3
-
-
?
ATP + MKK3
ADP + phosphorylated MKK3
-
activation of the p38 MAP kinase signaling pathway
-
-
?
ATP + MKK3
ADP + phosphorylated MKK3
-
activation of the p38 MAP kinase signaling pathway leading to apoptosis
-
-
?
ATP + MKK3
ADP + phosphorylated MKK3
a MAPKK, OMTK1 channels oxidative stress signaling through direct interaction with MAPK MMK3 increasing the cell death rate, OMTK1 and MMK3 form a complex in vivo
-
-
?
ATP + MKK3
ADP + phosphorylated MKK3
-
activation of the p38 MAP kinase signaling pathway leading to apoptosis
-
-
?
ATP + MKK4
ADP + phosphorylated MKK4
-
activation of the Jun N-terminal kinase, JNK, pathway leading to apoptosis
-
-
?
ATP + MKK4
ADP + phosphorylated MKK4
-
substrate of MEKK1 mutant Q1254E and of MTK1 mutant E1372Q
-
-
?
ATP + MKK4
ADP + phosphorylated MKK4
activated by ASK2 in complex with ASK1
-
-
?
ATP + MKK4
ADP + phosphorylated MKK4
-
activation of the Jun N-terminal kinase, JNK, pathway leading to apoptosis
-
-
?
ATP + MKK4
ADP + phosphorylated MKK4
-
MKK4 activates the JNK signaling pathway
-
-
?
ATP + MKK4
ADP + phosphorylated MKK4
-
a MAPKK, activity of wild-type and mutant MEKK1 with wild-type and mutant MKK4, determination of the MKK4 binding site of MEKK1, overview
-
-
?
ATP + MKK4
ADP + phosphorylated MKK4
-
a MAPKK, recombinant GST-tagged MKK4
-
-
?
ATP + MKK6
ADP + phosphorylated MKK6
substrate Brassica napus MAPK kinase 6
-
-
?
ATP + MKK6
ADP + phosphorylated MKK6
activation by MEKK3 of MAPK signaling pathways
-
-
?
ATP + MKK6
ADP + phosphorylated MKK6
-
activation of the p38 MAP kinase signaling pathway
-
-
?
ATP + MKK6
ADP + phosphorylated MKK6
-
activation of the p38 MAP kinase signaling pathway leading to apoptosis
-
-
?
ATP + MKK6
ADP + phosphorylated MKK6
-
substrate of stress-activated MAPKKKs ASK1 and MTK1
-
-
?
ATP + MKK6
ADP + phosphorylated MKK6
-
phosphorylation in the activation loop, substrate of stress-activated MAPKKKs ASK1 and MTK1, no activity with MKK6 mutants E318P, F327D, I331D, and V328G, but reduced activity with MKK6 mutants V324G and V328A
-
-
?
ATP + MKK6
ADP + phosphorylated MKK6
activated by ASK2 in complex with ASK1
-
-
?
ATP + MKK6
ADP + phosphorylated MKK6
-
activation of the p38 MAP kinase signaling pathway leading to apoptosis
-
-
?
ATP + MKK6
ADP + phosphorylated MKK6
-
phosphorylation of Ser526 is required for MKK6 phosphorylation in vitro
-
-
?
ATP + MKK7
ADP + phosphorylated MKK7
activation by MEKK3 of MAPK signaling pathways
-
-
?
ATP + MKK7
ADP + phosphorylated MKK7
-
activation of the Jun N-terminal kinase, JNK, signaling pathway leading to apoptosis
-
-
?
ATP + MKK7
ADP + phosphorylated MKK7
-
activation of the Jun N-terminal kinase, JNK, signaling pathway leading to apoptosis
-
-
?
ATP + MPK4
ADP + phosphorylated MPK4
MEKK1 is essential for MPK4 activation by flg22
-
-
?
ATP + myelin basic protein
ADP + phosphorylated myelin basic protein
-
-
-
-
?
ATP + myelin basic protein
ADP + phosphorylated myelin basic protein
-
-
-
?
ATP + myelin basic protein
ADP + phosphorylated myelin basic protein
-
-
-
-
?
ATP + myelin basic protein
ADP + phosphorylated myelin basic protein
-
-
-
?
ATP + p38
ADP + phosphorylated p38
activated by ASK2 in complex with ASK1
-
-
?
ATP + p38
ADP + phosphorylated p38
-
MEKK3-dependent activation correlates with a requirement for serine at position 526
-
-
?
ATP + p42 MAPK
ADP + phosphorylated p42 MAPK
-
Ras-induced activation of the MAPK signaling cascade
-
-
?
ATP + p42 MAPK
ADP + phosphorylated p42 MAPK
-
the substrate of B-Raf and C-Raf, no substrate of Mos, recombinant His6-p42 MAPK substrate
-
-
?
ATP + protein
ADP + phosphoprotein
selectively regulates the c-Jun amino terminal kinase pathway
-
-
?
ATP + protein
ADP + phosphoprotein
JSAP1 functions as a scaffold protein in the JNK3 cascade
-
-
?
ATP + protein
ADP + phosphoprotein
enzyme is involved in the response of haploid yeast cells to peptide mating pheromones
-
-
?
ATP + protein
ADP + phosphoprotein
the enzyme is required for cell-type-specific transcription and signal transduction
-
-
?
ATP + protein
ADP + phosphoprotein
required for activation of the MAPK homologue Spc1, and integrity of the Wis1-Spc1 pathway is required for survival in extreme conditions of heat, osmolarity, oxidation or limited nutrition. Phosphorylates Wis1 in vitro and activates it in vivo
-
-
?
ATP + protein
ADP + phosphoprotein
capable of partial suppression of the ras1 mutant phenotype
-
-
?
ATP + protein
ADP + phosphoprotein
phosphorylates and activates Wis1 MAP kinase kinase in response to high osmolarity
-
-
?
ATP + protein
ADP + phosphoprotein
ste8 gene product functions in the signal transduction pathway
-
-
?
ATP + protein
ADP + phosphoprotein
Mkh1 regulates cell morphology, cell wall integrity, salt resistance, cell cycle reentry from stationary-phase arrest, and filamentous growth in response to stress
-
-
?
ATP + Ror2
ADP + phospho-Ror2
TGF-beta activated kinase 1, a MAPKKK, interacts with Ror2 and phosphorylates its intracellular carboxyterminal serine/thronine/proline-rich, STP, domain, Wnt-ligand binding differentially controls the Ror2/TAK1 interaction, Ror2 seems to act as a Wnt co-receptor enhancing Wnt-dependent canonical pathways while Tyr- and Ser/Thr-phosphorylation of Ror2 negatively controls the efficiency of these pathways, overview
-
-
?
ATP + Ror2
ADP + phospho-Ror2
TAK1 phosphorylates Ror2, a receptor tyrosine kinase, at multiple sites, activity of TAK1 with Ror2 phosphorylation site mutants, overview
-
-
?
ATP + Sty1
ADP + phosphorylated Sty1
MAPK kinase Sty1 activation
-
-
?
ATP + Sty1
ADP + phosphorylated Sty1
MAPK kinase Sty1 activation
-
-
?
ATP + tristetraprolin
ADP + phosphorylated tristetraprolin
i.e. TTP, physical interaction of MEKK1 with TTP
-
-
?
additional information
?
-
-
stomatal development and pattern is controlled by YODA
-
-
?
additional information
?
-
-
activity of MEKK1 may not be required for flg22-induced MPK4, MPK3 or MPK6 activation or for other macroscopic FLS2-mediated responses
-
-
?
additional information
?
-
MEKK1 is dispensable for MPK3 and MPK6 activation by flg22
-
-
?
additional information
?
-
MKK1 and MKK2 interact with MEKK1 and MPK4 in vivo, and activation of MPK4 by flg22 requires MEKK1 as well as MKK1 and MKK2, suggesting that MEKK1, MKK1/MKK2, and MPK4 form a MAPK cascade to negatively regulate plant immune responses
-
-
?
additional information
?
-
MKK1 and MKK2 interact with MEKK1 and MPK4 in vivo, and activation of MPK4 by flg22 requires MEKK1 as well as MKK1 and MKK2, suggesting that MEKK1, MKK1/MKK2, and MPK4 form a MAPK cascade to negatively regulate plant immune responses
-
-
?
additional information
?
-
-
MKK1 and MKK2 interact with MEKK1 and MPK4 in vivo, and activation of MPK4 by flg22 requires MEKK1 as well as MKK1 and MKK2, suggesting that MEKK1, MKK1/MKK2, and MPK4 form a MAPK cascade to negatively regulate plant immune responses
-
-
?
additional information
?
-
MEKK2 interacts with MPK4 and is phosphorylated by MPK4 in vitro
-
-
?
additional information
?
-
MEKK2 interacts with MPK4 and is phosphorylated by MPK4 in vitro
-
-
?
additional information
?
-
-
MEKK2 interacts with MPK4 and is phosphorylated by MPK4 in vitro
-
-
?
additional information
?
-
Raf10 has autophosphorylation activity
-
-
?
additional information
?
-
Raf10 has autophosphorylation activity
-
-
?
additional information
?
-
Raf11 has autophosphorylation activity
-
-
?
additional information
?
-
Raf11 has autophosphorylation activity
-
-
?
additional information
?
-
Raf11 has autophosphorylation activity
-
-
?
additional information
?
-
Raf11 has autophosphorylation activity
-
-
?
additional information
?
-
Raf10 has autophosphorylation activity
-
-
?
additional information
?
-
Raf10 has autophosphorylation activity
-
-
?
additional information
?
-
MEKK2 interacts with MPK4 and is phosphorylated by MPK4 in vitro
-
-
?
additional information
?
-
MEKK2 interacts with MPK4 and is phosphorylated by MPK4 in vitro
-
-
?
additional information
?
-
MKK1 and MKK2 interact with MEKK1 and MPK4 in vivo, and activation of MPK4 by flg22 requires MEKK1 as well as MKK1 and MKK2, suggesting that MEKK1, MKK1/MKK2, and MPK4 form a MAPK cascade to negatively regulate plant immune responses
-
-
?
additional information
?
-
MKK1 and MKK2 interact with MEKK1 and MPK4 in vivo, and activation of MPK4 by flg22 requires MEKK1 as well as MKK1 and MKK2, suggesting that MEKK1, MKK1/MKK2, and MPK4 form a MAPK cascade to negatively regulate plant immune responses
-
-
?
additional information
?
-
-
identification and validation of BnaMAPKKK and BnaMKK interactions. BnaMKK1 and BnaMKK4 do not interact with any of the 28 BnaMAPKKK proteins assayed. Six BnaMAPKKKs, BnaMAPKKK17, -18, and -20, BnaZIK3 and -4, and BnaRaf35 interact with BnaMKK3. Six BnaMAPKKKs, BnaMAPKKK17, -19, -20, BnaZIK2, -9, and BnaRaf28, interact with BnaMKK9. Three BnaMAPKKKs, BnaZIK2, -9, and BnaRaf28, interact with BnaMKK5, and five BnaMAPKKKs, BnaMAPKKK17, -19, -20, BnaZIK2, and BnaRaf28 interact with BnaMKK8. As regards BnaMKK2 and -6, only BnaRaf28 interact with both of them
-
-
?
additional information
?
-
identification and validation of BnaMAPKKK and BnaMKK interactions. BnaMKK1 and BnaMKK4 do not interact with any of the 28 BnaMAPKKK proteins assayed. Six BnaMAPKKKs, BnaMAPKKK17, -18, and -20, BnaZIK3 and -4, and BnaRaf35 interact with BnaMKK3. Six BnaMAPKKKs, BnaMAPKKK17, -19, -20, BnaZIK2, -9, and BnaRaf28, interact with BnaMKK9. Three BnaMAPKKKs, BnaZIK2, -9, and BnaRaf28, interact with BnaMKK5, and five BnaMAPKKKs, BnaMAPKKK17, -19, -20, BnaZIK2, and BnaRaf28 interact with BnaMKK8. As regards BnaMKK2 and -6, only BnaRaf28 interact with both of them
-
-
?
additional information
?
-
identification and validation of BnaMAPKKK and BnaMKK interactions. BnaMKK1 and BnaMKK4 do not interact with any of the 28 BnaMAPKKK proteins assayed. Six BnaMAPKKKs, BnaMAPKKK17, -18, and -20, BnaZIK3 and -4, and BnaRaf35 interact with BnaMKK3. Six BnaMAPKKKs, BnaMAPKKK17, -19, -20, BnaZIK2, -9, and BnaRaf28, interact with BnaMKK9. Three BnaMAPKKKs, BnaZIK2, -9, and BnaRaf28, interact with BnaMKK5, and five BnaMAPKKKs, BnaMAPKKK17, -19, -20, BnaZIK2, and BnaRaf28 interact with BnaMKK8. As regards BnaMKK2 and -6, only BnaRaf28 interact with both of them
-
-
?
additional information
?
-
-
identification and validation of BnaMAPKKK and BnaMKK interactions. No interactions with BnaMKK1, BnaMKK2, BnaMKK4, BnaMKK5, BnaMKK6, BnaMKK8, and BnaMKK9. BnaMAPKKK18 interacts with MKK3
-
-
?
additional information
?
-
identification and validation of BnaMAPKKK and BnaMKK interactions. No interactions with BnaMKK1, BnaMKK2, BnaMKK4, BnaMKK5, BnaMKK6, BnaMKK8, and BnaMKK9. BnaMAPKKK18 interacts with MKK3
-
-
?
additional information
?
-
identification and validation of BnaMAPKKK and BnaMKK interactions. No interactions with BnaMKK1, BnaMKK2, BnaMKK4, BnaMKK5, BnaMKK6, BnaMKK8, and BnaMKK9. BnaMAPKKK18 interacts with MKK3
-
-
?
additional information
?
-
-
identification and validation of BnaMAPKKK and BnaMKK interactions. No interactions with BnaMKK1-BnaMKK6. BnaMAPKKK19 interacts with BnaMKK8 and with BnaMKK9 wild-type and mutants S193D/S199E and K74R. BnaMKK9S193D/S199E is constitutively active while the K74R mutant is constitutively inactive
-
-
?
additional information
?
-
identification and validation of BnaMAPKKK and BnaMKK interactions. No interactions with BnaMKK1-BnaMKK6. BnaMAPKKK19 interacts with BnaMKK8 and with BnaMKK9 wild-type and mutants S193D/S199E and K74R. BnaMKK9S193D/S199E is constitutively active while the K74R mutant is constitutively inactive
-
-
?
additional information
?
-
identification and validation of BnaMAPKKK and BnaMKK interactions. No interactions with BnaMKK1-BnaMKK6. BnaMAPKKK19 interacts with BnaMKK8 and with BnaMKK9 wild-type and mutants S193D/S199E and K74R. BnaMKK9S193D/S199E is constitutively active while the K74R mutant is constitutively inactive
-
-
?
additional information
?
-
-
NSY-1 functions in the control of asymmetric expression of odor receptor gene str-2, odor discrimination, and odor chemotaxis, thus possibly in functional differentiation of the nervous system, the enzyme functions downstream of UNC-43 CaMKII
-
-
?
additional information
?
-
-
MEKK4 is a signaling protein of the p38 MAPK pathway
-
-
?
additional information
?
-
-
enzyme is part of mitogen-activated protein kinase pathways, crosstalk and regulation mechanism, overview
-
-
?
additional information
?
-
-
activation mechanism of ASK1, overview, ASK1 is involved in oxidative stress-induced cell death and adaptation processes to various stresses, the enzyme is required for induction of apoptosis by e.g. Fas or TNF-alpha, or by the endoplasmic reticulum, mechanism, ASK1 plays an important role in neuropathological alterations in polyQ diseases
-
-
?
additional information
?
-
-
alterations of the intracellular milieu induced by methylglyoxal through a MEKK1-mediated and PI3K/PKC/Raf-1-independent pathway results in the modification of cell response to IGF-I for the cyclin-dependent kinase inhibitor p21_Waf1/Cip1-mediated growth arrest, which may be one of the crucial mechanisms for methylglyoxal to promote the development of chronic clinical complications in diabetes in humans
-
-
?
additional information
?
-
-
COT is a proto-oncogene, the enzyme is essential for the lipopolysaccharide activation of the ERK MAPK cascade in macrophages
-
-
?
additional information
?
-
Cot plays an important role in inflammation and oncogenesis, MEKK3 mediates the activation of JNK and ERK in the MAP kinase pathway and of the NF-kappaB pathway and mediates the interleukin-8 production, MEKK3 and Cot are negatively regulated by hKSR-2
-
-
?
additional information
?
-
-
Cot plays an important role in inflammation and oncogenesis, MEKK3 mediates the activation of JNK and ERK in the MAP kinase pathway and of the NF-kappaB pathway and mediates the interleukin-8 production, MEKK3 and Cot are negatively regulated by hKSR-2
-
-
?
additional information
?
-
-
DLK acts as a key regulator of keratinocyte terminal differentiation, and is involved in activation of the JNK signaling pathway, DLK activity is required for transglutaminase activation and induction of keratinocyte cornification
-
-
?
additional information
?
-
-
MEKK3 is involved in activation of MAPKs e.g. p38 and JNK
-
-
?
additional information
?
-
-
MEKK3 is involved in activation of NF-kappaB and increased expression of cell survival factors which confers resistance to apoptosis
-
-
?
additional information
?
-
-
MLTKalpha activates the p38gamma MAPK-dependent signaling pathway, which is regulated by the serine/threonine kinase PKNalpha
-
-
?
additional information
?
-
-
regulation, overview, Ras and mitogen-activated protein kinase kinase kinase-1 coregulate activator protein-1- and nuclear factor-kappaB-mediated gene expression in airway epithelial cells, the enzyme is involved in activation of the signaling cascades via activator protein AP-1 and NF-kappaB
-
-
?
additional information
?
-
-
the MAPKKKs are part of the MAPK signaling cascade, several structurally diverse MAPKKK families exist, overview
-
-
?
additional information
?
-
-
the natural enzyme mutant V599E induces cell transformation in NIH3T3 cells, the B-Raf/MEK/ERK pathway regulates cell cycle proteins, overview
-
-
?
additional information
?
-
-
no phosphorylation/activation of IkappaB kinase
-
-
?
additional information
?
-
-
substrate specificities of MAPKKKs with wild-type and mutant MAPKKs, overview, no activity with MKK7 by MEKK1 mutant Q1254E, wild-type MTK1, and MTK1 mutant E1372Q, the enzyme docks at the DVD docking site of MAPKK, a stretch of about 20 amino acids immediately on the C-terminal side of the catalytic domain, MAPKK with mutated DVD docking sites are inhibitory for the MAPKKK, overview
-
-
?
additional information
?
-
-
MEKK1-induced MMP-1promoter-driven luciferase activity is largely dependent on a c/EBPbeta-NF-kappaB-like enhancer site at -2008 to -1972 bp
-
-
?
additional information
?
-
-
MEKK4 is a signaling protein of the p38 MAPK pathway
-
-
?
additional information
?
-
-
RAF kinases exhibit high substrate selectivity, exclusively targeting the dual-specificity (Tyr/Thr) kinases MEK1/2
-
-
?
additional information
?
-
the OMTK1 kinase domain is involved in activation of signaling pathways in case of oxidative stress to induce cell death playing a MAPK scaffolding role, OMTK1 shows low constitutive activity
-
-
?
additional information
?
-
-
activation mechanism of ASK1, overview, ASK1 is involved in oxidative stress-induced cell death and adaptation processes to various stresses, the enzyme is required for induction of apoptosis by e.g. Fas or TNF-alpha, or by the endoplasmic reticulum, mechanism
-
-
?
additional information
?
-
-
alterations of the intracellular milieu induced by methylglyoxal through a MEKK1-mediated and PI3K/PKC/Raf-1-independent pathway results in the modification of cell response to IGF-I for the cyclin-dependent kinase inhibitor p21Waf1/Cip1-mediated growth arrest
-
-
?
additional information
?
-
-
MEKK2 and MEKK3 are involved in activation of signal transduction pathways via toll-like receptor TLR, mitogen-activated protein kinases MAPK, and NF-kappaB, overview
-
-
?
additional information
?
-
-
MEKK2 induces the JNK signaling pathway, overview
-
-
?
additional information
?
-
-
the enzyme is part of the MAPK signaling cascades, overview
-
-
?
additional information
?
-
-
the MAPKKKs are part of the MAPK signaling cascade, overview, MEKK1 regulates calpain-dependent cell migration via regulation of th ERK2-dependent signaling pathway and binding to focal adhesions, actinin, and FAK, overview
-
-
?
additional information
?
-
-
the enzyme docks at the DVD docking site of MAPKK, a stretch of about 20 amino acids immediately on the C-terminal side of the catalytic domain, MAPKK with mutated DVD docking sites are inhibitory for the MAPKKK
-
-
?
additional information
?
-
-
endogenous MEKK3 is phosphorylated on Ser526 in the response to exogenous stimuli like osmotic stress
-
-
?
additional information
?
-
-
MEKK3 is required for IL-1R and LPS-induced IL-6 production in fibroblasts
-
-
?
additional information
?
-
-
MEKK4 is a signaling protein of the p38 MAPK pathway
-
-
?
additional information
?
-
-
induces activation of NF-kappaB reporter activity, deficiency cells show defects in TNFalpha signalling
-
-
?
additional information
?
-
-
involved in the activation of NF-kappaB, negatively regulates MEKK3-induced activation of NF-kappaB reporter activity, able to autophosphorylate at multiple sites when bound to TAB1, deficiency cells show defects in TNFalpha signalling
-
-
?
additional information
?
-
-
phosphorylates and activates MAP kinase kinase, activates ERK and JNK pathways in cells of the imune system in response to inflammatory mediators, knockout mice show normal development but defects in inflammatory response, involved in T-cell proliferation, probably involved in cardiac myocyte differentiation
-
-
?
additional information
?
-
-
phosphorylates and activates MAP kinase kinase, activates ERK1/2 and possibly also ERK3, important function in vascular development, important physiological role in cell growth and development, related to oncogenesis
-
-
?
additional information
?
-
-
phosphorylates and activates MAP kinase kinase, activates JNK and p38MAP kinases in response to stress stimuli, knockout mice usually dying shortly after birth due to neural tube and skeletal malformations, functions in regulation of apoptosis and cell migration, possibly acts as central regulator of calcium-mediated signaling
-
-
?
additional information
?
-
-
phosphorylates and activates MAP kinase kinase, activates JNK during neuronal migration in cerebal cortex development
-
-
?
additional information
?
-
-
phosphorylates and activates MAP kinase kinase, activates the p38 pathway in response to stress and DNA damage
-
-
?
additional information
?
-
-
phosphorylates and activates MAP kinase kinase, appears to transduce signals for JNK and ERK1/2 activation by pro-inflammatory stimuli and growth factors, key regulator of cell migration, deletion mutants are viable and fertile but display altered migration of epithelial cells resulting in defective eyelid closure, enzyme interacts directly with MEK1, MEK2 and c-Raf, involved in oxidative stress induced apoptosis in cardiac myocytes, enzyme deficiency individuals have diminished B-cell numbers, directly and indirectly involved in cell migration
-
-
?
additional information
?
-
-
phosphorylates and activates MAP kinase kinase, important for the transduction of survival signals, involved in the regulation of apoptosis, important for TGFbeta signalling, deletion mutation in adult mice results in bone marrow and liver failure due to increased apoptosis of hematopoetic cells and hepatocytes, embryonic deletion is lethal due to severe vascular defects and delayed growth
-
-
?
additional information
?
-
-
phosphorylates and activates MAP kinase kinase, induces the activation of the MEK/ERK pathway, important physiological role in cell growth and development, related to oncogenesis
-
-
?
additional information
?
-
-
phosphorylates and activates MAP kinase kinase, involved in cellular stress response and JNK and p38 pathway activation, MLK1, 2 and 3 knockout mice show no obvious abnormalities, MLK 7 is activated in response to stressors like anisomycin and UV radiation and activates pro-apoptotic pathways through p38 and JNK
-
-
?
additional information
?
-
-
phosphorylates and activates MAP kinase kinase, regulates apoptosis in response to stress stimuli, knockout mice do not exhibit developmental defects, activates p38 and JNK pathways
-
-
?
additional information
?
-
-
phosphorylates and activates MAP kinase kinase, regulates p38,ERK1/2 and JNK, knockout embryos dying in utero due to abnormalities in vessel development and heart development, key regulator of cardiovascular and nervous system formation
-
-
?
additional information
?
-
-
phosphorylates and activates MAP kinase kinase, regulation of apoptosis, induction of the MEK/ERK pathway, promotes cell survival in the heart through modulation of MEKK5 activity, important physiological role in cell growth and development, related to oncogenesis
-
-
?
additional information
?
-
-
phosphorylates and activates MAP kinase kinase, selctive for the activation of JNK and ERK5, knockout mutants are viable and fertile without apparent malformations, involved in T-cell receptor modulation and cytokine production in response to IgE
-
-
?
additional information
?
-
-
involved in the regulation of development and secondary metabolism, deficiency mutant forms short aerial hyphae, show reduced formation of asexual macroconidia, and reduced growth
-
-
?
additional information
?
-
MAPKKKalpha is responsible for hypersensitive response and resistance to Pseudomonas syringae infection, the enzyme also regulates cell death in susceptible, infected leaves, identification of MAPKKKalpha-induced signal cascades, regulation, overview
-
-
?
additional information
?
-
-
possible mechanismof ILA1 action, interaction analysis with possible substrate proteins, overview
-
-
?
additional information
?
-
-
the enzyme is involved in cell signaling and controls cell degeneration and cell differentiation and thus regulating development and pathogenicity sensing the external conditions
-
-
?
additional information
?
-
-
involved in maintaining cell wall integrity, remodeling of the cell wall in response to host environments is essential for fungal pathogenesis
-
-
?
additional information
?
-
-
MEKK1 and ASK1 might play opposing roles in oxidative stress-induced activation of apoptosis
-
-
?
additional information
?
-
-
Ste11 is involved in MAPK pathway signal transduction governing mating, osmoregulation, and nitrogen starvation by direct interaction with the sterile alpha motif domains, SAM, of Ste50 and Ste11
-
-
?
additional information
?
-
-
Ste50 binds the MAPKKK Ste11 through a head-to-tail sterile interaction via both alpha motif SAM domains, NMR binding study, very tight and stable binding between the two mutants Ste50 L69R and Ste11 L72R, overview
-
-
?
additional information
?
-
-
activator of the Pbs2 MAPKK in the SLN1 branch of the Hog1 MAPK cascade, involved in osmoregulation
-
-
?
additional information
?
-
MAPKKKalpha is responsible for hypersensitive response and resistance to pathogen infection, the enzyme also regulates cell death in susceptible leaves after infection, overview
-
-
?
additional information
?
-
-
N-CoR is refractory to MAPKKK signaling, alternative splicing of N-CoR has only minimal effects on the resistance of this corepressor to MAPKKK inhibition
-
-
?
additional information
?
-
-
B-Raf and C-Raf, but not Mos, are required for Ras-induced MEK1 and p42 MAPK activation
-
-
?
additional information
?
-
-
MLK2 plays a tissue specific role and is required for cement gland development and nephritic tubule formation, MLK2 mediates the response of Jun N-terminal kinase JNK, i.e. stress-activated protein kinase 1 SAPK1, to UV irradiation
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + c-Jun
ADP + phosphorylated c-Jun
MAP3K1 phosphorylates and activates a JNK-c-Jun module
-
-
?
ATP + ERK5
ADP + phosphorylated ERK5
-
substrate of MEKK2 and MEKK3, activation of the ERK-dependent signaling pathway
-
-
?
ATP + GLI1
ADP + phosphorylated GLI1
-
mitogen-activated kinase kinase kinase 1 phosphorylates the C-terminal region of GLI1
-
-
?
ATP + MEK2
ADP + phosphorylated MEK2
activation by MEKK3 of MAPK signaling pathways
-
-
?
ATP + MKK
ADP + phosphorylated MKK
-
induction of the JNK pathway activation
-
-
?
ATP + p42 MAPK
ADP + phosphorylated p42 MAPK
-
Ras-induced activation of the MAPK signaling cascade
-
-
?
ATP + Ror2
ADP + phospho-Ror2
TGF-beta activated kinase 1, a MAPKKK, interacts with Ror2 and phosphorylates its intracellular carboxyterminal serine/thronine/proline-rich, STP, domain, Wnt-ligand binding differentially controls the Ror2/TAK1 interaction, Ror2 seems to act as a Wnt co-receptor enhancing Wnt-dependent canonical pathways while Tyr- and Ser/Thr-phosphorylation of Ror2 negatively controls the efficiency of these pathways, overview
-
-
?
BAD + ATP
BAD-phosphate + ADP
-
activation of the proapoptotic protein BAD
-
-
?
MAP2K + ATP
MAP2K-phosphate + ADP
-
involved in reducing c-jun N-terminal kinase (JNK, MAPK8) activation and protecting the mice from nickel-induced acute lung injury
-
-
?
MEK-1 + ATP
phosphorylated MEK-1 + ADP
-
essential step of the MAP-kinase cascade, activation of MEK-1 which is a MAPKK, essential role in vegetative hyphal growth, conidiation and protoperithecial development, as well as a more limited involvement in maintenance of cell wall integrity, not essential for the resistance to osmotic stress, negatively regulates tyrosinase expression
-
-
?
ATP + Atf1
ADP + phosphorylated Atf1
MAPK kinase Atf1 activation
-
-
?
ATP + Atf1
ADP + phosphorylated Atf1
MAPK kinase Atf1 activation
-
-
?
ATP + BcSak1
ADP + phosphorylated BcSak1
BcSak1 is a putative downstream component of BcOs4
-
-
?
ATP + BcSak1
ADP + phosphorylated BcSak1
BcSak1 is a putative downstream component of BcOs4
-
-
?
ATP + ERK
ADP + phosphorylated ERK
-
i.e. extracellular signal-regulated kinase
-
-
?
ATP + ERK
ADP + phosphorylated ERK
-
PI3K/PKC/Raf-1-independent activation of the MEK/ERK signaling pathway
-
-
?
ATP + ERK
ADP + phosphorylated ERK
-
PI3K/PKC/Raf-1-independent activation of the MEK/ERK signaling pathway
-
-
?
ATP + MEK
ADP + phosphorylated MEK
-
PI3K/PKC/Raf-1-independent activation of the MEK/ERK signaling pathway
-
-
?
ATP + MEK
ADP + phosphorylated MEK
-
PI3K/PKC/Raf-1-independent activation of the MEK/ERK signaling pathway
-
-
?
ATP + MEK1
ADP + phosphorylated MEK1
activation by MEKK3 of MAPK signaling pathways
-
-
?
ATP + MEK1
ADP + phosphorylated MEK1
-
MEK1 activates the ERK2 signaling pathway
-
-
?
ATP + MEK1
ADP + phosphorylated MEK1
-
Ras-induced activation of the MAPK signaling cascade
-
-
?
ATP + MKK1
ADP + phosphorylated MKK1
-
MKK1 activates the ERK2 signaling pathway
-
-
?
ATP + MKK3
ADP + phosphorylated MKK3
substrate Brassica napus MAPK kinase 3
-
-
?
ATP + MKK3
ADP + phosphorylated MKK3
-
activation of the p38 MAP kinase signaling pathway
-
-
?
ATP + MKK3
ADP + phosphorylated MKK3
-
activation of the p38 MAP kinase signaling pathway leading to apoptosis
-
-
?
ATP + MKK3
ADP + phosphorylated MKK3
a MAPKK, OMTK1 channels oxidative stress signaling through direct interaction with MAPK MMK3 increasing the cell death rate, OMTK1 and MMK3 form a complex in vivo
-
-
?
ATP + MKK3
ADP + phosphorylated MKK3
-
activation of the p38 MAP kinase signaling pathway leading to apoptosis
-
-
?
ATP + MKK4
ADP + phosphorylated MKK4
-
activation of the Jun N-terminal kinase, JNK, pathway leading to apoptosis
-
-
?
ATP + MKK4
ADP + phosphorylated MKK4
-
activation of the Jun N-terminal kinase, JNK, pathway leading to apoptosis
-
-
?
ATP + MKK4
ADP + phosphorylated MKK4
-
MKK4 activates the JNK signaling pathway
-
-
?
ATP + MKK6
ADP + phosphorylated MKK6
substrate Brassica napus MAPK kinase 6
-
-
?
ATP + MKK6
ADP + phosphorylated MKK6
activation by MEKK3 of MAPK signaling pathways
-
-
?
ATP + MKK6
ADP + phosphorylated MKK6
-
activation of the p38 MAP kinase signaling pathway
-
-
?
ATP + MKK6
ADP + phosphorylated MKK6
-
activation of the p38 MAP kinase signaling pathway leading to apoptosis
-
-
?
ATP + MKK6
ADP + phosphorylated MKK6
-
substrate of stress-activated MAPKKKs ASK1 and MTK1
-
-
?
ATP + MKK6
ADP + phosphorylated MKK6
-
activation of the p38 MAP kinase signaling pathway leading to apoptosis
-
-
?
ATP + MKK7
ADP + phosphorylated MKK7
activation by MEKK3 of MAPK signaling pathways
-
-
?
ATP + MKK7
ADP + phosphorylated MKK7
-
activation of the Jun N-terminal kinase, JNK, signaling pathway leading to apoptosis
-
-
?
ATP + MKK7
ADP + phosphorylated MKK7
-
activation of the Jun N-terminal kinase, JNK, signaling pathway leading to apoptosis
-
-
?
ATP + myelin basic protein
ADP + phosphorylated myelin basic protein
-
-
-
?
ATP + protein
ADP + phosphoprotein
selectively regulates the c-Jun amino terminal kinase pathway
-
-
?
ATP + protein
ADP + phosphoprotein
JSAP1 functions as a scaffold protein in the JNK3 cascade
-
-
?
ATP + protein
ADP + phosphoprotein
enzyme is involved in the response of haploid yeast cells to peptide mating pheromones
-
-
?
ATP + protein
ADP + phosphoprotein
the enzyme is required for cell-type-specific transcription and signal transduction
-
-
?
ATP + protein
ADP + phosphoprotein
required for activation of the MAPK homologue Spc1, and integrity of the Wis1-Spc1 pathway is required for survival in extreme conditions of heat, osmolarity, oxidation or limited nutrition. Phosphorylates Wis1 in vitro and activates it in vivo
-
-
?
ATP + protein
ADP + phosphoprotein
capable of partial suppression of the ras1 mutant phenotype
-
-
?
ATP + protein
ADP + phosphoprotein
phosphorylates and activates Wis1 MAP kinase kinase in response to high osmolarity
-
-
?
ATP + protein
ADP + phosphoprotein
ste8 gene product functions in the signal transduction pathway
-
-
?
ATP + protein
ADP + phosphoprotein
Mkh1 regulates cell morphology, cell wall integrity, salt resistance, cell cycle reentry from stationary-phase arrest, and filamentous growth in response to stress
-
-
?
ATP + Sty1
ADP + phosphorylated Sty1
MAPK kinase Sty1 activation
-
-
?
ATP + Sty1
ADP + phosphorylated Sty1
MAPK kinase Sty1 activation
-
-
?
additional information
?
-
-
stomatal development and pattern is controlled by YODA
-
-
?
additional information
?
-
MKK1 and MKK2 interact with MEKK1 and MPK4 in vivo, and activation of MPK4 by flg22 requires MEKK1 as well as MKK1 and MKK2, suggesting that MEKK1, MKK1/MKK2, and MPK4 form a MAPK cascade to negatively regulate plant immune responses
-
-
?
additional information
?
-
MKK1 and MKK2 interact with MEKK1 and MPK4 in vivo, and activation of MPK4 by flg22 requires MEKK1 as well as MKK1 and MKK2, suggesting that MEKK1, MKK1/MKK2, and MPK4 form a MAPK cascade to negatively regulate plant immune responses
-
-
?
additional information
?
-
-
MKK1 and MKK2 interact with MEKK1 and MPK4 in vivo, and activation of MPK4 by flg22 requires MEKK1 as well as MKK1 and MKK2, suggesting that MEKK1, MKK1/MKK2, and MPK4 form a MAPK cascade to negatively regulate plant immune responses
-
-
?
additional information
?
-
MKK1 and MKK2 interact with MEKK1 and MPK4 in vivo, and activation of MPK4 by flg22 requires MEKK1 as well as MKK1 and MKK2, suggesting that MEKK1, MKK1/MKK2, and MPK4 form a MAPK cascade to negatively regulate plant immune responses
-
-
?
additional information
?
-
MKK1 and MKK2 interact with MEKK1 and MPK4 in vivo, and activation of MPK4 by flg22 requires MEKK1 as well as MKK1 and MKK2, suggesting that MEKK1, MKK1/MKK2, and MPK4 form a MAPK cascade to negatively regulate plant immune responses
-
-
?
additional information
?
-
-
NSY-1 functions in the control of asymmetric expression of odor receptor gene str-2, odor discrimination, and odor chemotaxis, thus possibly in functional differentiation of the nervous system, the enzyme functions downstream of UNC-43 CaMKII
-
-
?
additional information
?
-
-
enzyme is part of mitogen-activated protein kinase pathways, crosstalk and regulation mechanism, overview
-
-
?
additional information
?
-
-
activation mechanism of ASK1, overview, ASK1 is involved in oxidative stress-induced cell death and adaptation processes to various stresses, the enzyme is required for induction of apoptosis by e.g. Fas or TNF-alpha, or by the endoplasmic reticulum, mechanism, ASK1 plays an important role in neuropathological alterations in polyQ diseases
-
-
?
additional information
?
-
-
alterations of the intracellular milieu induced by methylglyoxal through a MEKK1-mediated and PI3K/PKC/Raf-1-independent pathway results in the modification of cell response to IGF-I for the cyclin-dependent kinase inhibitor p21_Waf1/Cip1-mediated growth arrest, which may be one of the crucial mechanisms for methylglyoxal to promote the development of chronic clinical complications in diabetes in humans
-
-
?
additional information
?
-
-
COT is a proto-oncogene, the enzyme is essential for the lipopolysaccharide activation of the ERK MAPK cascade in macrophages
-
-
?
additional information
?
-
Cot plays an important role in inflammation and oncogenesis, MEKK3 mediates the activation of JNK and ERK in the MAP kinase pathway and of the NF-kappaB pathway and mediates the interleukin-8 production, MEKK3 and Cot are negatively regulated by hKSR-2
-
-
?
additional information
?
-
-
Cot plays an important role in inflammation and oncogenesis, MEKK3 mediates the activation of JNK and ERK in the MAP kinase pathway and of the NF-kappaB pathway and mediates the interleukin-8 production, MEKK3 and Cot are negatively regulated by hKSR-2
-
-
?
additional information
?
-
-
DLK acts as a key regulator of keratinocyte terminal differentiation, and is involved in activation of the JNK signaling pathway, DLK activity is required for transglutaminase activation and induction of keratinocyte cornification
-
-
?
additional information
?
-
-
MEKK3 is involved in activation of MAPKs e.g. p38 and JNK
-
-
?
additional information
?
-
-
MEKK3 is involved in activation of NF-kappaB and increased expression of cell survival factors which confers resistance to apoptosis
-
-
?
additional information
?
-
-
MLTKalpha activates the p38gamma MAPK-dependent signaling pathway, which is regulated by the serine/threonine kinase PKNalpha
-
-
?
additional information
?
-
-
regulation, overview, Ras and mitogen-activated protein kinase kinase kinase-1 coregulate activator protein-1- and nuclear factor-kappaB-mediated gene expression in airway epithelial cells, the enzyme is involved in activation of the signaling cascades via activator protein AP-1 and NF-kappaB
-
-
?
additional information
?
-
-
the MAPKKKs are part of the MAPK signaling cascade, several structurally diverse MAPKKK families exist, overview
-
-
?
additional information
?
-
-
the natural enzyme mutant V599E induces cell transformation in NIH3T3 cells, the B-Raf/MEK/ERK pathway regulates cell cycle proteins, overview
-
-
?
additional information
?
-
the OMTK1 kinase domain is involved in activation of signaling pathways in case of oxidative stress to induce cell death playing a MAPK scaffolding role, OMTK1 shows low constitutive activity
-
-
?
additional information
?
-
-
activation mechanism of ASK1, overview, ASK1 is involved in oxidative stress-induced cell death and adaptation processes to various stresses, the enzyme is required for induction of apoptosis by e.g. Fas or TNF-alpha, or by the endoplasmic reticulum, mechanism
-
-
?
additional information
?
-
-
alterations of the intracellular milieu induced by methylglyoxal through a MEKK1-mediated and PI3K/PKC/Raf-1-independent pathway results in the modification of cell response to IGF-I for the cyclin-dependent kinase inhibitor p21Waf1/Cip1-mediated growth arrest
-
-
?
additional information
?
-
-
MEKK2 and MEKK3 are involved in activation of signal transduction pathways via toll-like receptor TLR, mitogen-activated protein kinases MAPK, and NF-kappaB, overview
-
-
?
additional information
?
-
-
MEKK2 induces the JNK signaling pathway, overview
-
-
?
additional information
?
-
-
the enzyme is part of the MAPK signaling cascades, overview
-
-
?
additional information
?
-
-
the MAPKKKs are part of the MAPK signaling cascade, overview, MEKK1 regulates calpain-dependent cell migration via regulation of th ERK2-dependent signaling pathway and binding to focal adhesions, actinin, and FAK, overview
-
-
?
additional information
?
-
-
endogenous MEKK3 is phosphorylated on Ser526 in the response to exogenous stimuli like osmotic stress
-
-
?
additional information
?
-
-
induces activation of NF-kappaB reporter activity, deficiency cells show defects in TNFalpha signalling
-
-
?
additional information
?
-
-
involved in the activation of NF-kappaB, negatively regulates MEKK3-induced activation of NF-kappaB reporter activity, able to autophosphorylate at multiple sites when bound to TAB1, deficiency cells show defects in TNFalpha signalling
-
-
?
additional information
?
-
-
phosphorylates and activates MAP kinase kinase, activates ERK and JNK pathways in cells of the imune system in response to inflammatory mediators, knockout mice show normal development but defects in inflammatory response, involved in T-cell proliferation, probably involved in cardiac myocyte differentiation
-
-
?
additional information
?
-
-
phosphorylates and activates MAP kinase kinase, activates ERK1/2 and possibly also ERK3, important function in vascular development, important physiological role in cell growth and development, related to oncogenesis
-
-
?
additional information
?
-
-
phosphorylates and activates MAP kinase kinase, activates JNK and p38MAP kinases in response to stress stimuli, knockout mice usually dying shortly after birth due to neural tube and skeletal malformations, functions in regulation of apoptosis and cell migration, possibly acts as central regulator of calcium-mediated signaling
-
-
?
additional information
?
-
-
phosphorylates and activates MAP kinase kinase, activates JNK during neuronal migration in cerebal cortex development
-
-
?
additional information
?
-
-
phosphorylates and activates MAP kinase kinase, activates the p38 pathway in response to stress and DNA damage
-
-
?
additional information
?
-
-
phosphorylates and activates MAP kinase kinase, appears to transduce signals for JNK and ERK1/2 activation by pro-inflammatory stimuli and growth factors, key regulator of cell migration, deletion mutants are viable and fertile but display altered migration of epithelial cells resulting in defective eyelid closure, enzyme interacts directly with MEK1, MEK2 and c-Raf, involved in oxidative stress induced apoptosis in cardiac myocytes, enzyme deficiency individuals have diminished B-cell numbers, directly and indirectly involved in cell migration
-
-
?
additional information
?
-
-
phosphorylates and activates MAP kinase kinase, important for the transduction of survival signals, involved in the regulation of apoptosis, important for TGFbeta signalling, deletion mutation in adult mice results in bone marrow and liver failure due to increased apoptosis of hematopoetic cells and hepatocytes, embryonic deletion is lethal due to severe vascular defects and delayed growth
-
-
?
additional information
?
-
-
phosphorylates and activates MAP kinase kinase, induces the activation of the MEK/ERK pathway, important physiological role in cell growth and development, related to oncogenesis
-
-
?
additional information
?
-
-
phosphorylates and activates MAP kinase kinase, involved in cellular stress response and JNK and p38 pathway activation, MLK1, 2 and 3 knockout mice show no obvious abnormalities, MLK 7 is activated in response to stressors like anisomycin and UV radiation and activates pro-apoptotic pathways through p38 and JNK
-
-
?
additional information
?
-
-
phosphorylates and activates MAP kinase kinase, regulates apoptosis in response to stress stimuli, knockout mice do not exhibit developmental defects, activates p38 and JNK pathways
-
-
?
additional information
?
-
-
phosphorylates and activates MAP kinase kinase, regulates p38,ERK1/2 and JNK, knockout embryos dying in utero due to abnormalities in vessel development and heart development, key regulator of cardiovascular and nervous system formation
-
-
?
additional information
?
-
-
phosphorylates and activates MAP kinase kinase, regulation of apoptosis, induction of the MEK/ERK pathway, promotes cell survival in the heart through modulation of MEKK5 activity, important physiological role in cell growth and development, related to oncogenesis
-
-
?
additional information
?
-
-
phosphorylates and activates MAP kinase kinase, selctive for the activation of JNK and ERK5, knockout mutants are viable and fertile without apparent malformations, involved in T-cell receptor modulation and cytokine production in response to IgE
-
-
?
additional information
?
-
-
involved in the regulation of development and secondary metabolism, deficiency mutant forms short aerial hyphae, show reduced formation of asexual macroconidia, and reduced growth
-
-
?
additional information
?
-
MAPKKKalpha is responsible for hypersensitive response and resistance to Pseudomonas syringae infection, the enzyme also regulates cell death in susceptible, infected leaves, identification of MAPKKKalpha-induced signal cascades, regulation, overview
-
-
?
additional information
?
-
-
possible mechanismof ILA1 action, interaction analysis with possible substrate proteins, overview
-
-
?
additional information
?
-
-
the enzyme is involved in cell signaling and controls cell degeneration and cell differentiation and thus regulating development and pathogenicity sensing the external conditions
-
-
?
additional information
?
-
-
involved in maintaining cell wall integrity, remodeling of the cell wall in response to host environments is essential for fungal pathogenesis
-
-
?
additional information
?
-
-
MEKK1 and ASK1 might play opposing roles in oxidative stress-induced activation of apoptosis
-
-
?
additional information
?
-
-
Ste11 is involved in MAPK pathway signal transduction governing mating, osmoregulation, and nitrogen starvation by direct interaction with the sterile alpha motif domains, SAM, of Ste50 and Ste11
-
-
?
additional information
?
-
-
activator of the Pbs2 MAPKK in the SLN1 branch of the Hog1 MAPK cascade, involved in osmoregulation
-
-
?
additional information
?
-
MAPKKKalpha is responsible for hypersensitive response and resistance to pathogen infection, the enzyme also regulates cell death in susceptible leaves after infection, overview
-
-
?
additional information
?
-
-
B-Raf and C-Raf, but not Mos, are required for Ras-induced MEK1 and p42 MAPK activation
-
-
?
additional information
?
-
-
MLK2 plays a tissue specific role and is required for cement gland development and nephritic tubule formation, MLK2 mediates the response of Jun N-terminal kinase JNK, i.e. stress-activated protein kinase 1 SAPK1, to UV irradiation
-
-
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ATP
-
-
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
additional information
-
no or nearly no activity with Ni2+, Zn2+, Co2+, and Cu2+
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(E)-N-(4-((4-ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)-phenyl)-3-(2-(4-methoxy-1H-pyrrolo[2,3-b]pyridin-5-yl)vinyl)-4-methylbenzamide
-
88,5% inhibition of TAK1 at 500 nM
2-amino-1-{4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}-2-[4-methyl-3-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)phenyl]ethanone
-
-
3-((1H-pyrrolo[2,3-b]pyridin-4-yl)oxy)-N-(4-((4-ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)-4-methylbenzamide
-
a type II inhibitor, 97.1% inhibition of TAK1 at 500 nM
3-[(6,7-dimethoxyquinazolin-4-yl)oxy]-N-{4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}-4-methylbenzamide
-
83.7% inhibition of TAK1 at 0.001 mM
4-methyl-3-{[6-(methylamino)pyrimidin-4-yl]oxy}-N-[3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl]benzamide
-
selectivity analysis with diverse enzymes, overview. 29.3% Inhibition of TAK1 at 0.001 mM
4-methyl-3-{[6-(methylamino)pyrimidin-4-yl]oxy}-N-[3-(4-methylpiperazin-1-yl)-5-(trifluoromethyl)phenyl]benzamide
-
selectivity analysis with diverse enzymes, overview. 7.0% Inhibition of TAK1 at 0.001 mM
4-methyl-N-[3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl]-3-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)benzamide
-
-
4-methyl-N-[3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl]-3-[2-(1H-pyrrolo[2,3-b]pyridin-4-yl)ethyl]benzamide
-
-
4-methyl-N-[3-(4-methylpiperazin-1-yl)-5-(trifluoromethyl)phenyl]-3-(7H-pyrrolo[2,3-d]pyrimidin-4-yloxy)benzamide
-
29.3% inhibition of TAK1 at 0.001 mM
4-methyl-N-{4-[(1-methylpiperidin-4-yl)oxy]-3-(trifluoromethyl)phenyl}-3-[(E)-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)ethenyl]benzamide
-
-
4-[(4-ethylpiperazin-1-yl)methyl]-N-{3-[2-(1H-pyrrolo[2,3-b]pyridin-4-yl)ethyl]phenyl}-3-(trifluoromethyl)benzamide
-
-
4-[5-({4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}carbamoyl)-2-methylphenoxy]-N-methylpyridine-2-carboxamide
-
-
CEP-1347
-
inhibits MLKs and is well tolerated in human trials, does not perform in trials for neurodegenerative disorders such as Parkinson´s disease
farnesylthiosalicylic acid
-
a Ras antagonist, inhibits the wild-type and V599E mutant enzyme in vivo and in vitro
hKSR-2
i.e. human kinase suppressor of ras 2, selectively inhibits MEKK3-activated MAP kinase and NF-kappaB pathways in inflammation, selectively inhibits Cot, no inhibition of MEKK4, TAK1, and Ras-Raf
-
menadione
-
i.e. 2-methyl-1,4-naphthoquinone, oxidative stress caused by menadione inhibits MEKK1, which can be reversed by DTT and glutathione, inhibition is thus caused by a reversible Cys1238 oxidation mechanism followed by binding to glutathione, no inhibition of MEKK1 mutant C1238V
N-ethylmaleimide
-
MEKK1 inhibition through Cys1238 alkylation, Cys1238 is located in the ATP binding domain, no inhibition of MEKK1 mutant C1238V
N-[3-(2-cyanopropan-2-yl)phenyl]-4-methyl-3-[(E)-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)ethenyl]benzamide
-
-
N-[3-(2-cyanopropan-2-yl)phenyl]-4-methyl-3-[2-(1H-pyrrolo[2,3-b]pyridin-4-yl)ethyl]benzamide
-
-
N-[4-{[3-(dimethylamino)pyrrolidin-1-yl]methyl}-3-(trifluoromethyl)phenyl]-4-methyl-3-[(E)-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)ethenyl]benzamide
-
-
N-{4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}-3-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)benzamide
-
75.6% inhibition of TAK1 at 0.001 mM
N-{4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}-3-[(E)-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)ethenyl]benzamide
-
-
N-{4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}-3-[2-(1H-pyrrolo[2,3-b]pyridin-4-yl)ethyl]benzamide
-
-
N-{4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}-4-methyl-3-(1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)benzamide
-
77.7% inhibition of TAK1 at 0.001 mM; 86.5% inhibition of TAK1 at 0.001 mM
N-{4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}-4-methyl-3-(1H-pyrrolo[2,3-b]pyridin-4-ylmethoxy)benzamide
-
59.6% inhibition of TAK1 at 0.001 mM
N-{4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}-4-methyl-3-[(2-methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)oxy]benzamide
-
57.7% inhibition of TAK1 at 0.001 mM
N-{4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}-4-methyl-3-[2-(1H-pyrrolo[2,3-b]pyridin-4-yl)ethyl]benzamide
-
74.3% inhibition of TAK1 at 0.001 mM
N-{4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}-4-methyl-3-{[2-(methylamino)pyrimidin-4-yl]oxy}benzamide
-
77.7% inhibition of TAK1 at 0.001 mM
N-{4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}-4-methyl-3-{[6-(methylamino)pyrimidin-4-yl]oxy}benzamide
-
78.5% inhibition of TAK1 at 0.001 mM
N-{4-[(4-ethylpiperazin-1-yl)methyl]phenyl}-4-methyl-3-[(E)-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)ethenyl]benzamide
-
-
SB203580
-
does not relieve the inhibitory effect of MEKK1 on insulin gene transcription, although it effectively decreases phosphorylation of JNK, SAPK/p38 or ERK, respectively
SP600125
-
does not relieve the inhibitory effect of MEKK1 on insulin gene transcription, although it effectively decreases phosphorylation of JNK, SAPK/p38 or ERK, respectively
BAY 43-9006
-
c-Raf inhibitor, shows promising response rate in patients with primary renal cell carcinomas
p105
-
inhibition of COT activity, but binding of p105 increases the solubility and stability of COT
-
siRNA
-
MEKK1-specific siRNA inhibits with adenovirus-mediated overexpression of melanoma differentiation-associated gene-7-mediated MEKK1 cleavage
-
siRNA
transfection of siRNA for ASK1 into cells reduces expression of not only ASK1 but also ASK2
-
U0126
-
inhibits MEKK2/MEKK3-dependent ERK5 phosphorylation/activation in vitro and in vivo
U0126
-
does not relieve the inhibitory effect of MEKK1 on insulin gene transcription, although it effectively decreases phosphorylation of JNK, SAPK/p38 or ERK, respectively
additional information
suppression of mekk1 phenotypes at high temperature
-
additional information
no inhibition of Raf10 by the MAP2K inhibitor U0126; no inhibition of Raf11 by the MAP2K inhibitor U0126
-
additional information
no inhibition of Raf10 by the MAP2K inhibitor U0126; no inhibition of Raf11 by the MAP2K inhibitor U0126
-
additional information
-
MAPKK with mutated DVD docking sites are inhibitory for the MAPKKK, as well as synthetic DVD sequence oligopeptides of e.g. MKK6, in vitro and in vivo, overview
-
additional information
-
prostaglandin E2, wild-type p53 expression in the presence of prostaglandin E2, and p53S15E suppress steady-state levels of MEKK1-induced interstitial collagenase MMP-1 mRNA, effects nullified with co-transfection of p53 dnm or p53S15A. Prostaglandin E2, overexpression of p53wt with prostaglandin E2, or p53S15E abolish MEKK1-induced MMP-1 promoter luciferase activity
-
additional information
-
sFRP-1 significantly impairs Wnt3a-conditioned-media-induced activation of GCKR
-
additional information
-
discovery of type II inhibitors of TGFbeta-activated kinase 1 (TAK1), a series of 4-substituted 1H-pyrrolo[2,3-b]pyridines exhibit potent inhibitory activity against mitogen-activated protein kinase TAK1 (MAP3K7), overview. Identification of potent dual TAK1 and MAP4K2 inhibitors such as 1 (NG25) and 2 as well as MAP4K2 selective inhibitors such as 16 and 17. The activation loop of TAK1 assumes the DFG-out conformation characteristic of type II inhibitors. Inhibitor binding structure analysis, docking using the enzyme crystal structure, overview
-
additional information
-
RAF kinases are inhibited by autoinhibitory domains, which precludes dimerization of the kinase domain and renders the enzyme inactive
-
additional information
-
MAPKK with mutated DVD docking sites are inhibitory for the MAPKKK, as well as synthetic DVD sequence oligopeptides in vitro and in vivo, overview
-
additional information
-
ubiquitinylation of MEKK1 inhibits the enzyme in vitro and in vivo
-
additional information
-
MEKK1 down-regulation by interfering RNA significantly delays skin wound closure and impairs activation of Jun NH2-terminal kinases, induction of plasminogen activator inhibitor 1, and restoration of cell-cell junctions of the wounded epidermis
-
additional information
-
sFRP-1 significantly impairs Wnt3a-conditioned-media-induced activation of GCKR
-
additional information
-
inactive in vivo when bound to MEKK3; inactive in vivo when bound to TAK1
-
additional information
-
inhibitory function within the N-terminal domain
-
additional information
-
incubation of MEKK1 with phosphoprotein phosphatases 2A dephosphorylates the protein, significantly reducing the basal activity of MEKK1 generated from insect cells
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Gadd45alpha
-
causes an increase in the activation of both the p38 and JNK pathways, but not the ERK pathway, upregulates MEKK4s kinase activity to a lesser degree as compared to Gadd45beta or Gadd45gamma
-
Gadd45beta
-
causes an increase in the activation of both the p38 and JNK pathways, but not the ERK pathway
-
Gadd45gamma
-
causes an increase in the activation of both the p38 and JNK pathways, but not the ERK pathway
-
GTPAse Rac1
-
interacts with MLK2, the enzyme contains a G-protein binding domain, i.e. a CRIB domain
-
osomolarity two-component system protein SSK1
-
non-phosphorylated dimer, binding of Ssk1 seems to be necessary for Ssk2 activation
-
Ste50
-
Ste50 binding of the MAPKKK Ste11 through a head-to-tail sterile interaction via both alpha motif SAM domains is required for Ste11 activity and cell viability, NMR binding study, very tight and stable binding between the two mutants Ste50 L69R and Ste11 L72R, molecular modeling, overview
-
H2O2
-
activates, MEKK1 kinase activity and protein stability is regulated by H2O2 in a proteasome-dependent manner
H2O2
phosphorylation of ASK2 at Thr807 increases in response to H2O2 in cells co-expressing ASK2 and a ASK1 kinase-negative mutant, whereas singly expressed ASK2 does not respond to H2O2. ASK2 kinase-negative mutant co-expressed with ASK1 kinase-negative mutant is not phosphorylated at Thr807 irrespective of the H2O2 treatment
methylglyoxal
-
induces the PI3K/PKC/Raf-1-independent MEK/ERK signaling pathway by activation of MEKK1, accumulates in case of diabetes
methylglyoxal
-
induces the PI3K/PKC/Raf-1-independent MEK/ERK signaling pathway by activation of MEKK1, accumulates in case of diabetes
Ras
-
required for maximal activity in ERK and JNK phosphorylation/activation and for activation of AP-1 pathway
-
Ras
-
the interaction of the two oncoproteins RAS and BRAF is absolutely required for activation of the MAPK pathway, binding structure analysis, detailed overview. Allosteric conformational changes upon RAS binding, propagated through the beta-sheet and alpha-helical core of the protein domain.Changes in BRAF RAS-binding domain (RBD) that accompany RAS binding provide a basis for allosteric regulation of BRAF structure and function, and suggest a mechanism by which RAS binding can signal domain rearrangements required for activation of BRAF kinase
-
TNF-alpha
-
treatment with TNF-alpha dissociates the inhibitor thioredoxin from the enzyme's N-terminus
-
TNF-alpha
-
treatment with TNF-alpha dissociates the inhibitor thioredoxin from the enzyme's N-terminus
-
Wnt3a
-
induces GCKR kinase activity. APC, Asef, and Rac are required for Wnt signaling to activate GCKR
-
Wnt3a
-
induces GCKR kinase activity. APC, Asef, and Rac are required for Wnt signaling to activate GCKR
-
additional information
-
a functional DVD docking site of MAPKK substrates is absolutely required for activity
-
additional information
-
MEKK2 and MEKK3 are phosphorylated and thereby activated by kinase WNK1
-
additional information
-
MLTKalpha is activated by phosphorylation through PKNalpha
-
additional information
-
phosphorylation at Ser526 and Thr530 in the activation loop is required for MEKK3 activation, dephosphorylation is blocked by binding to protein 14-3-3
-
additional information
-
polymerization and phosphorylation activates the enzyme after dissociation of thioredoxin due to TNF-alpha treatment
-
additional information
-
RhoA L63, the active mutant of RhoA, dramatically stimulates the activity of endogenous MEKK1, whereas RhoA wild-type and RhoA N19, a dominant negative mutant of RhoA, show little activation effect
-
additional information
-
treatment of H1299-dnIkappaBalpha tumors with adenovirus-mediated overexpression of melanoma differentiation-associated gene-7 shows increased MEKK1 cleavage and activation of caspase-3, induces NF-kappaB expression in lung tumor cells in a time-dependent manner. NF-kappaB activation by overexpressed dnIkappaBalpha enhances the antitumor activity of melanoma differentiation-associated gene-7
-
additional information
-
dimerization through the catalytic domain is essential for MEKK2 activation
-
additional information
-
MEKK1 forms complexes with FAK involved in regulation of cell migration, overview
-
additional information
-
polymerization and phosphorylation activates the enzyme after dissociation of thioredoxin due to TNF-alpha treatment
-
additional information
-
full-thickness skin injury markedly stimulates MEKK1 expression and activity
-
additional information
-
MEKK1 containing residues 1-719 interacts with wild-type RhoA. MEKK1 (149-636) also associates with wild-type RhoA in yeast. The constitutively active mutant of RhoA, RhoAL63, also binds to residues 149-636, whereas the inactive mutant RhoAN19 fails to bind any of the MEKK1 fragments. Interaction between RhoA and MEKK1 seems to be activation-dependent (GTP-binding dependent) in yeast
-
additional information
-
no change in phosphorylation of Ser526 in the presence or absence of okadaic acid
-
additional information
-
Ssk1p binds and activates the MEKK kinases Ssk2p and Ssk22p, de-phosphorylated Ssk1p binds to the N-terminal auto-inhibitory domain of Ssk2p and Ssk22p, activating their auto-phosphorylation on a conserved threonine residue
-
additional information
-
stimulation of MEKK1 kinase activity by RhoA in vitro
-
additional information
-
UV irradiation increases the enzyme activity, no interaction with Cdc42 and RhoA by MLK2
-
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
kinetics of binding between wild-type and mutant Ste11 and wild-type and mutant Ste50, overview
-
0.03
ATP
-
recombinant COT30-397/p105DELTAN and recombinant COT30-467/p105DELTAN, pH 7.5, 22°C, with 5 mM Mn2+
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
large scale activity assay with recombinant enzyme in a protein chip consisting of a microwell array with protein covalently attached to the wells via a 3-glycidoxypropyltrimethoxysilane crosslinker, overview
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.4
7.5
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
22
25
30
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TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
4.74 - 9.42
diverse MAPKKK enzymes, equence calculations, overview
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
i.e. Botryotinia fuckeliana, strain 38B1 is isolated from a grape in California, USA, and deposited to the China Microbiological Culture Collection Center, accession number CGMCC no. 4006
UniProt
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i.e. Botryotinia fuckeliana, strain 38B1 is isolated from a grape in California, USA, and deposited to the China Microbiological Culture Collection Center, accession number CGMCC no. 4006
UniProt
brenda
disruption of MCK1 resulted in the fungus undergoing autolysis and showing hypersensitivity to cell-wall-degrading enzyme, mutant strain produces significantly reduced numbers of conidia and developed appressoria in a slightly retarded manner compared with the wild type, mutant is unable to penetrate into plant tissues
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activity requires TAB1 (TAK1 binding protein), binding of TAB1 promotes autophosphorylation of TAK1
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native and mutant mice, mutant embryos are growth retarded and die in utero
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normal and mutant mice, mutant mice appear normal at birth but die 7-21 days postpartum due to neurological and intestinal problems
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normal and mutant mice, mutant mice die in utero due to severe vascular abnormalities
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wild type embryonic fibroblast and cells with a MAP3K deletion used for experiments
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
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MLK2 expression correlates with cell elongation and the onset of an apoptotic phase
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highest expression. In pigs, isoform MAP3K8 expression is higher in mature corpus luteums (or those of the mid-luteal phase) than in regressing corpus luteums (late luteal phase)
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preferential expression of MEKK1 in the vasculature
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MAP3K1 is highly expressed in the developing eyelid tip epithelial cells before eyelid closure
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the enzyme is most abundantly expressed in developing nervous tissues
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embryo, MLK2 expression correlates with the differentiation and opening of the nephritic tubules, but not with apoptosis
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prior to fertilization, strongest FRK2 mRNA accumulation
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Tpl-2 isolated from Moloney leukemia virus-induced thymoma cells
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additional information
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MEKK4 mRNA is detected from stages embryonic day 8.5 through 14.5 encompassing prelooped, looping, cushion morphogenesis, and completed septation stages of heart development. MEKK4 protein is detected to the developing heart at stages embryonic day 10.5 to 14.5
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no changes in B-Raf activity in the first embryonic cell cycles
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detection of MEKK4 transcripts to early myocardium, endocardium and to cardiac cushion cells that have executed epithelial to mesenchymal transformation
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DLK acts as a key regulator of keratinocyte terminal differentiation and cornification
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MEKK1 binds to the promoter of the WRKY53 gene regulating the switch from a leaf age dependent to a plant age dependent expression
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no changes in B-Raf activity during progesterone-induced maturation
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strong expression in pollen grains increasing from young buds to later stages of maturation
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Raf11 promoter activity is observed in embryos and most of the seedling tissues, except emerging leaves and root tips, Raf11 expression patterns, overview
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Raf11 promoter activity is observed in embryos and most of the seedling tissues, except emerging leaves and root tips, Raf11 expression patterns, overview
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prior to fertilization, strongest FRK2 mRNA accumulation
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MLK2 expression from late gastrula stage/early neurula stage on
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additional information
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stomatal development and pattern is controlled by YODA
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additional information
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under normal conditions, kinases MKKK20, MKK3 and MPK20 are weakly expressed in all tissues
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additional information
under normal conditions, kinases MKKK20, MKK3 and MPK20 are weakly expressed in all tissues
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additional information
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expression patterns of roots, stems, and leaves, overview. 68 MAPKKK proteins encoded by 63 MAPKKK genes (22 MEKK subfamily members, 38 Raf subfamily members, and 3 ZIK subfamily members) are detected. BdMAPKKK genes expression patterns at different developmental stage tissues, two visualized hierarchy cluster of different developmental stages and organs are constructed
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additional information
mixed lineage kinase 4 (MLK4) is overexpressed in mesenchymal but not proneural glioma stem cells, GSCs
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additional information
ovule, strong up-regulation of FRK2 after fertilization, FRK2 mRNAs accumulate during early ovule development in the megasporocyte and in the integument of developing ovules
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additional information
ovule, strong up-regulation of FRK2 after fertilization, FRK2 mRNAs accumulate during early ovule development in the megasporocyte and in the integument of developing ovules
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additional information
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ovule, strong up-regulation of FRK2 after fertilization, FRK2 mRNAs accumulate during early ovule development in the megasporocyte and in the integument of developing ovules
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additional information
enzyme FRK1 shows a highly specific expression profile following fertilization. The ScFRK1 gene is expressed early on during female gametophyte development in the integument and megaspore mother cell and, later, in the synergid and egg cells of the embryo sac. Strong ScFRK1 mRNA accumulation is only observed in the ovary and, to a lesser extent, in the style. ScFRK1 is expressed in both the sporophyte and the gametophyte. No ScFRK1 mRNA signal is detected in mature pollen, but a strong signal is observed in crosssections of flower buds in the anthers. Expression patterns, overview
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additional information
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enzyme FRK1 shows a highly specific expression profile following fertilization. The ScFRK1 gene is expressed early on during female gametophyte development in the integument and megaspore mother cell and, later, in the synergid and egg cells of the embryo sac. Strong ScFRK1 mRNA accumulation is only observed in the ovary and, to a lesser extent, in the style. ScFRK1 is expressed in both the sporophyte and the gametophyte. No ScFRK1 mRNA signal is detected in mature pollen, but a strong signal is observed in crosssections of flower buds in the anthers. Expression patterns, overview
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additional information
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tissue-specific expression of MLK2, no or very low expression in liver, lung, heart, muscle, and kidney
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
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MEKK1/WRKY53 complexes are predominantly localized in the nucleus
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additional information
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subcellular locations of MAKKK proteins in Brachypodium distachyon
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additional information
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subcellular distribution of MAPKKK proteins, overview
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additional information
subcellular distribution of MAPKKK proteins, overview
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additional information
subcellular distribution of MAPKKK proteins, overview
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additional information
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ectopic expression of B-Raf in cutaneous melanoma cells
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additional information
localized to perinuclear, vesicular compartment similar to the Golgi
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additional information
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localized to perinuclear, vesicular compartment similar to the Golgi
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additional information
analysis of cellular localization of the ScFRK1 kinase, overview
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additional information
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analysis of cellular localization of the ScFRK1 kinase, overview
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
metabolism
physiological function
additional information
evolution
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bioinformatics analysis of the entire maize genome identifies 74 MAPKKK genes. Phylogenetic analyses of MAPKKKs from maize, rice and Arabidopsis classifies them into three subgroups, which include Raf, ZIK and MEKK. Evolutionary relationships within subfamilies are supported by exon-intron organizations and the conserved protein motifs
evolution
enzyme FRK1 belongs to a small group of pMEKKs that do not possess an extended N- or C-terminal regulatory domain
evolution
gene BnaMAPKKK18 belongs to the MEKK subfamily of the MAPKKK family, phylogenetic and domain analysis of MAPKKK genes in Brassica napus and compaarison to MAPKKK enzymes from Arabidopsis thaliana and Oryza sativa, overview
evolution
gene BnaMAPKKK19 belongs to the MEKK subfamily of the MAPKKK family, phylogenetic and domain analysis of MAPKKK genes in Brassica napus and compaarison to MAPKKK enzymes from Arabidopsis thaliana and Oryza sativa, overview
evolution
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identification of 86 MAPKKK proteins encoded by 73 MAPKKK genes in Brachypodium. Phylogenetic analysis of MAPKKK family from Arabidopsis, rice, and Brachypodium classifies them into three subfamilies, of which 28 belong to MEKK, 52 to Raf, and 6 to ZIK subfamily, respectively. Conserved protein motif, exon-intron organization, and splicing intron phase in kinase domains support the evolutionary relationships inferring from the phylogenetic analysis. Gene duplication analysis suggests the chromosomal segment duplication happened before the divergence of the rice and Brachypodium, while all of three tandem duplicated gene pairs happened after their divergence. Coexpression network of MAPK, MAPKK, and MAPKKK in Brachypodium and evolutionary and functional characterization of MAPKKK family in Brachypodium, gene duplication, especially chromosomal segment duplication act vital roles in MAPKKK gene expansion in Brachypodium distachyon, overview
evolution
mitogen-activated protein kinase kinase kinase gene BcOS4 in Botrytis cinerea is homologous to Saccharomyces cerevisiae SSK2/SSK22
evolution
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mitogen-activated protein kinase kinase kinases (MAPKKKs) kinase cascades are clustered into three groups A-C, ILA1 is a functional kinase of the group C Raf-like MAPKKK family, phylogenetic tree of ILA1 and other MAPKKKs in plants, overview
evolution
subfamilyiesof the MAPKKK family, phylogenetic and domain analysis of MAPKKK genes in Brassica napus and compaarison to MAPKKK enzymes from Arabidopsis thaliana and Oryza sativa, overview
evolution
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the enzyme belongs to the RAF (rapidly accelerated fibrosarcoma) kinase family
evolution
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mitogen-activated protein kinase kinase kinase gene BcOS4 in Botrytis cinerea is homologous to Saccharomyces cerevisiae SSK2/SSK22
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malfunction
analysis of mekk1 sid2 and mkk1 mkk2 sid2 mutant plants reveals that the elevated salicylic acid levels contribute very little to the mutant phenotypes in mekk1 and mkk1 mkk2
malfunction
decreased MAP3K1 expression causes delayed eyelid closure in Map3k1 hemizygotes. MAP3K1 inactivation reduces AP-1 activity and PAI-1 expression both in cells and developing eyelids
malfunction
in cadmium and low glucose medium, Atf1 activation is observed even in the absence of all four fission yeast MAPK kinase kinases (MAPKKKs), whereas in osmotic stress, Atf1 activation is abolished
malfunction
mice deficient in ZPK have twice as many spinal motoneurons as do their wild-type littermates. Nuclear HB9/MNX1-positive motoneuron pools are generated similarly in the spinal cord of both ZPK/DLK-deficient and wild-type embryos. Significantly less apoptotic motoneurons are found in ZPK/DLK-deficient embryos compared to wild-type embryos, resulting in retention of excess numbers of motoneurons after birth. The excess motoneurons remain viable without atrophic changes in the ZPK/DLK-deficient mice surviving into adulthood. Analysis of the diaphragm and the phrenic nerve reveals that clustering and innervation of neuromuscular junctions are indistinguishable between ZPK/DLK-deficient and wild-type mice, whereas the proximal portion of the phrenic nerve of ZPK/DLK-deficient mice contain significantly more axons than the distal portion. Some excess ZPK/DLK-deficient motoneurons survive without atrophy despite failure to establish axonal contact with their targets
malfunction
mutation of either MEKK1 or TRAF2 impairs TTP ubiquitination, whereas mutation of both completely abolishes TTP ubiquitination
malfunction
mutations in MEKK2 encoding suppressor of mkk1 mkk2 1 (summ1) gene suppress the cell death and defense responses not only in mkk1 mkk2 but also in mekk1 and mpk4. Overexpression of SUMM1 activates cell death and defense responses that are dependent on the nucleotide binding-leucine-rich repeat protein SUMM2. Pathogen resistance in mutants mkk1 mkk2 is affected by the summ1 mutation, e.g. versus oomycete pathogen Hyaloperonospora arabidopsidis Noco2
malfunction
on mutating either of the four crucial hydrophobic residues (Leu7, Ile10, Leu14, and Leu17) to charged Asp or substituting the conserved Asp13 to Ala in MEKK3, the binding between CCM2ct and MEKK3nt is completely abolished. Mutation of the nonconserved Glu3 of MEKK3 to Ala induced only 2fold reduction of the binding affinity between CCM2ct and MEKK3nt
malfunction
the abscisic acid-insensitive mutant, ais143, located in the coding region of MAP3K gene Raf10, abolishes RAF10 expression in the mutant. ais143 exhibits reduced seed dormancy as well as reduced abscisic acid sensitivity. The phenotypes are complemented by the wild-type Raf10 gene, and the overexpression of Raf10 results in delayed seed germination and enhanced the abscisic acid sensitivity. Raf11 knockout and overexpression lines show that their phenotypes are similar to those of Raf10 knockout and overexpression lines. An ais143 raf11 double mutant exhibits stronger phenotypes than single mutants, indicating the functional redundancy between Raf10 and Raf11. Expression of many abscisic acid-associated genes, including the key regulatory genes ABI3 and ABI5, is altered in the Raf10 and Raf11 overexpressing lines. Reduced seed dormancy of ais143 and raf11, overview. Both germination and cotyledon greening of ais143 and ais143 raf11 plants are less sensitive to high salt compared to wild-type
malfunction
the BcOS4 deletion mutant is significantly impaired in vegetative growth and conidial formation. The mutant exhibits increased sensitivity to the osmotic, oxidative stresses and to the fungicides iprodione and fludioxonil. BcSak1, a putative downstream component of BcOs4, is not phosphorylated in the mutant. The BcOS4 mutant is unable to infect leaves of rapeseed and cucumber, and grape fruits, although it can cause disease on apple fruits. The mutant strain exhibits increased sensitivity to the dicarboximide fungicide iprodione and the phenylpyrrole fungicide fludioxonil. All the defects are restored by genetic complementation of the BcOS4 deletion mutant with the wild-type BcOS4 gene. Phenotype of the BcOS4 deletion mutant, overview
malfunction
transgenic plants with lower or barely detectable levels of ScFRK1 mRNAs show production of small fruits with severely reduced seed set, resulting from a concomitant decline in the number of normal embryo sacs produced. Megagametogenesis and microgametogenesis are affected, as megaspores do not progress beyond the functional megaspore (FG1) stage and the microspore collapses around the first pollen mitosis. As for other mutants that affect embryo sac development, pollen tube guidance is severely affected in the ScFRK1 transgenic lines. Gametophyte to sporophyte communication is also affected, as observed from a marked change in the transcriptomic profiles of the sporophytic tissues of the ovule
malfunction
silencing MLK4 suppresses self-renewal, motility, tumorigenesis, and radioresistance of mesenchymal glioma stem cells via a loss of the mesenchymal signature. Silencing MLK4 inhibits de novo and acquired (radiation-induced) mesenchymal glioma stem cells both in vitro and in vivo. Silencing MLK4 attenuates mesenchymal identity in glioma stem cells. Depletion of MLK4 attenuates a set of mesenchymal glioma stem cell phenotypes
malfunction
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decreasing the expression of isoforms FRK1 and FRK3 leads to embryonic sac development arrest at the functional megaspore stage. Early ovule development is observed in isoforms FRK1 and FRK3 knockdown mutants, in which most ovules are arrested at the functional megaspore stage
malfunction
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enzyme deletion leads to a significant defect in growth and development. An enzyme-deficient mutant shows higher sensitivity to cell-wall stress than wild type. The pathogenicity of the enzyme-deficient Aspergillus flavus mutant is markedly reduced in peanut seed
malfunction
isoform MAP4K3 siRNA knockdown inhibits myotube formation and both MyoD and myogenin expression in primary preterm rat skeletal muscle satellite cells, but MAP4K3 siRNA has no effect on the activity of target of rapamycin complex 1. In primary preterm rat skeletal muscle satellite cells, isoform MAP4K3 knockdown results in significantly weaker, but not entirely blunted, leucine-induced target of rapamycin complex 1 signaling
malfunction
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the double knockout mutant of RAF22 and RAF28 is embryo lethal. Mutant embryos exhibit various defects, including disordered proembryo cell divisions, disruption of the bilaterally symmetrical structure, abnormally formative divisions of hypophysis and exaggerated suspensor growth
malfunction
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in cadmium and low glucose medium, Atf1 activation is observed even in the absence of all four fission yeast MAPK kinase kinases (MAPKKKs), whereas in osmotic stress, Atf1 activation is abolished
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malfunction
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the abscisic acid-insensitive mutant, ais143, located in the coding region of MAP3K gene Raf10, abolishes RAF10 expression in the mutant. ais143 exhibits reduced seed dormancy as well as reduced abscisic acid sensitivity. The phenotypes are complemented by the wild-type Raf10 gene, and the overexpression of Raf10 results in delayed seed germination and enhanced the abscisic acid sensitivity. Raf11 knockout and overexpression lines show that their phenotypes are similar to those of Raf10 knockout and overexpression lines. An ais143 raf11 double mutant exhibits stronger phenotypes than single mutants, indicating the functional redundancy between Raf10 and Raf11. Expression of many abscisic acid-associated genes, including the key regulatory genes ABI3 and ABI5, is altered in the Raf10 and Raf11 overexpressing lines. Reduced seed dormancy of ais143 and raf11, overview. Both germination and cotyledon greening of ais143 and ais143 raf11 plants are less sensitive to high salt compared to wild-type
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malfunction
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mutations in MEKK2 encoding suppressor of mkk1 mkk2 1 (summ1) gene suppress the cell death and defense responses not only in mkk1 mkk2 but also in mekk1 and mpk4. Overexpression of SUMM1 activates cell death and defense responses that are dependent on the nucleotide binding-leucine-rich repeat protein SUMM2. Pathogen resistance in mutants mkk1 mkk2 is affected by the summ1 mutation, e.g. versus oomycete pathogen Hyaloperonospora arabidopsidis Noco2
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malfunction
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analysis of mekk1 sid2 and mkk1 mkk2 sid2 mutant plants reveals that the elevated salicylic acid levels contribute very little to the mutant phenotypes in mekk1 and mkk1 mkk2
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malfunction
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the BcOS4 deletion mutant is significantly impaired in vegetative growth and conidial formation. The mutant exhibits increased sensitivity to the osmotic, oxidative stresses and to the fungicides iprodione and fludioxonil. BcSak1, a putative downstream component of BcOs4, is not phosphorylated in the mutant. The BcOS4 mutant is unable to infect leaves of rapeseed and cucumber, and grape fruits, although it can cause disease on apple fruits. The mutant strain exhibits increased sensitivity to the dicarboximide fungicide iprodione and the phenylpyrrole fungicide fludioxonil. All the defects are restored by genetic complementation of the BcOS4 deletion mutant with the wild-type BcOS4 gene. Phenotype of the BcOS4 deletion mutant, overview
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metabolism
a MAPK cascade is a signaling module usually consisting of a MAP kinase kinase kinase (MAPKKK), a MAP kinase kinase, and a MAPK. Activation of MAPKKKs by upstream signals results in sequential phosphorylation of their downstream MAPKKs and MAPKs. In Arabidopsis thaliana, the MEKK1-MKK1/MKK2-MPK4 mitogen-activated protein (MAP) kinase cascade represses cell death and immune responses. MEKK1, MKK1/MKK2, and MPK4 negatively regulate cell death and immunity. The MEKK1-MKK1/MKK2-MPK4 kinase cascade negatively regulates MEKK2 and activation of MEKK2 triggers SUMM2-mediated immune responses
metabolism
a MAPK cascade is a signaling module usually consisting of a MAP kinase kinase kinase (MAPKKK), a MAP kinase kinase, and a MAPK. Activation of MAPKKKs by upstream signals results in sequential phosphorylation of their downstream MAPKKs and MAPKs. The MEKK1-MKK1/MKK2-MPK4 kinase cascade negatively regulates MEKK2 and activation of MEKK2 triggers SUMM2-mediated immune responses. Mutants summ1-1 mkk1 mkk2 and summ1-2 mkk1 mkk2 exhibit wild type-like morphology
metabolism
MAPKK kinase family enzymes play important roles in plant growth, development and immune responses. The two downstream kinases MKK3 and MKK6 act in the BnaMAPKKK4 signaling pathway
metabolism
MEKK1 but not p38alpha abrogates TTP-mediated down-regulation of NF-kappaB activity. MEKK1-mediated N-terminal TTP phosphorylation is prerequisite for nondegradative TTP ubiquitination of its zinc finger. TTP is involved in TNFalpha-induced phosphorylation of JNK
metabolism
mitogen-activated protein kinase (MAPK) signalling cascades, consisting of three types of reversibly phosphorylated kinases (MAPKKK, MAPKK, and MAPK), are involved in important processes including plant immunity and hormone responses. The MAPKKKs comprise the largest family in the MAPK cascades
metabolism
mitogen-activated protein kinase kinase kinase 1 (MAP3K1) forms with c-Jun a regulatory axis that orchestrates morphogenesis by integrating two different networks of eyelid closure signals. TGF-alpha/EGFR-RhoA module initiates one of these networks by inducing c-Jun expression which, in a phosphorylation-independent manner, binds to the Map3k1 promoter and causes an increase in MAP3K1 expression. RhoA knockout in the ocular surface epithelium disturbs this network by decreasing MAP3K1 expression, and causes delayed eyelid closure in Map3k1 hemizygotes. The second network is initiated by the enzymatic activity of MAP3K1, which phosphorylates and activates a JNK-c-Jun module, leading to AP-1 transactivation and induction of its downstream genes, such as Pai-1
metabolism
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mitogen-activated protein kinase kinase kinases (MAPKKKs) function at the top level of mitogen-activated protein kinase cascades
metabolism
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predicted MAPK cascades with their three main members MAPKKK, MKK, and MPK with the same subcellular localization, overview
metabolism
the four MAPKKKs in fission yeast are involved in MAPK activation, e.g. Atf1 or Sty1, in osmotic stress. Osmotic stress, e.g. by KCl, likely mediates the MAPK activation via MAPKKKs, whereas a cadmium or low-glucose condition activates the MAPK in a MAPKKK-independent manner. Protein-tyrosine phosphatases Pyp1 and Pyp2 are negative regulators of the Sty1 MAPK cascade
metabolism
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the interaction of the two oncoproteins RAS and BRAF is absolutely required for activation of the MAPK pathway, binding structure analysis, overview
metabolism
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mitogen-activated kinase kinase kinase 1 suppresses hedgehog signalling by associating and phosphorylating GLI1, the most potent hedgehogx1eregulated transcription factor
metabolism
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the enzyme negatively regulates aflatoxin biosynthesis and is involved in the activation of the Slt2-MAPK pathway
metabolism
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the four MAPKKKs in fission yeast are involved in MAPK activation, e.g. Atf1 or Sty1, in osmotic stress. Osmotic stress, e.g. by KCl, likely mediates the MAPK activation via MAPKKKs, whereas a cadmium or low-glucose condition activates the MAPK in a MAPKKK-independent manner. Protein-tyrosine phosphatases Pyp1 and Pyp2 are negative regulators of the Sty1 MAPK cascade
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metabolism
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a MAPK cascade is a signaling module usually consisting of a MAP kinase kinase kinase (MAPKKK), a MAP kinase kinase, and a MAPK. Activation of MAPKKKs by upstream signals results in sequential phosphorylation of their downstream MAPKKs and MAPKs. The MEKK1-MKK1/MKK2-MPK4 kinase cascade negatively regulates MEKK2 and activation of MEKK2 triggers SUMM2-mediated immune responses. Mutants summ1-1 mkk1 mkk2 and summ1-2 mkk1 mkk2 exhibit wild type-like morphology
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metabolism
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a MAPK cascade is a signaling module usually consisting of a MAP kinase kinase kinase (MAPKKK), a MAP kinase kinase, and a MAPK. Activation of MAPKKKs by upstream signals results in sequential phosphorylation of their downstream MAPKKs and MAPKs. In Arabidopsis thaliana, the MEKK1-MKK1/MKK2-MPK4 mitogen-activated protein (MAP) kinase cascade represses cell death and immune responses. MEKK1, MKK1/MKK2, and MPK4 negatively regulate cell death and immunity. The MEKK1-MKK1/MKK2-MPK4 kinase cascade negatively regulates MEKK2 and activation of MEKK2 triggers SUMM2-mediated immune responses
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physiological function
MEKK3 is a central intermediate signaling component in lysophosphatidic acid-induced activation of the nuclear factor-kappa B
physiological function
activation of mitogen-activated protein kinase pathways is critically involved in naturally occurring programmed cell death of motoneurons during development. Enzyme ZPK, also called DLK, (ZPK/DLK), a mitogen-activated protein kinase kinase kinase, is a critical mediator of programmed cell death of motoneurons. The enzyme has a distinctive role in neural development and in naturally occurring programmed cell death
physiological function
BnaMAPKKK plays a role in the cross-talk of multiple stresses, including both abiotic and biotic stresses, overview. BnaMAPKKK18 elicits hypersensitive response (HR)-like cell death when transiently expressed in Nicotiana benthamiana leaves
physiological function
BnaMAPKKK plays a role in the cross-talk of multiple stresses, including both abiotic and biotic stresses, overview. BnaMAPKKK19 elicits hypersensitive response (HR)-like cell death when transiently expressed in Nicotiana benthamiana leaves. Gene BnaMAPKKK19 probably mediates cell death through MAPK kinase BnaMKK9.
physiological function
cerebral cavernous malformation 2 (CCM2) functions as an adaptor protein implicated in various biological processes. By interacting with the mitogen-activated protein kinase MEKK3, CCM2 either mediates the activation of MEKK3 signaling in response to osmotic stress or negatively regulates MEKK3 signaling, which is important for normal cardiovascular development
physiological function
expression of MAPKKK4 elicits reactive oxgen species, ROS, i.e. H2O2 accumulation and cell death. Upregulation of enzyme MAPKKK4 leads to increased expression of ROS accumulation, cell death, and defense response related genes
physiological function
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increased leaf angle1, a Raf-like MAPKKK that interacts with a nuclear protein family, regulates mechanical tissue formation in the Lamina joint of rice. ILA1 regulates mechanical strength in the leaf lamina joint affecting the leaf angle
physiological function
MAP3K1 is the nexus of an intracrine regulatory loop connecting the TGF-alpha/EGFR/RhoA-c-Jun and JNK-c-Jun-AP-1 pathways in developmental eyelid closure. the kinase activity of MAP3K1 is required for activation of the JNK-c-Jun pathway, induction of AP-1 activity, and PAI-1 expression during eyelid development. RhoA is an accessory to MAP3K1 signaling
physiological function
MAPKKK functions in biotic and abiotic stress responses in Brassica napus, overview
physiological function
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MAPKKKs are involved in important signaling pathways in maize different organs and developmental stages
physiological function
MEKK1 is involved in negative regulation of cell death and immunity
physiological function
mitogen-activated protein (MAP) kinase cascades are universal signaling modules in eukaryotes, which relay external or internal upstream signals to downstream targets. Arabidopsis thaliana putative MAP kinase kinase kinases Raf10 and Raf11 are positive regulators of seed dormancy and abscisic acid response
physiological function
mitogen-activated protein (MAP) kinase cascades are universal signaling modules in eukaryotes, which relay external or internal upstream signals to downstream targets. Arabidopsis thaliana putative MAP kinase kinase kinases Raf10 and Raf11 are positive regulators of seed dormancy. Raf11 plays a redundant role in abscisic acid response
physiological function
mitogen-activated protein kinase kinase kinase BcOs4 is required for vegetative differentiation and pathogenicity in Botrytis cinerea. BcOS4 is involved in vegetative differentiation, virulence, adaption to hyperosmotic and oxidative stresses, and to fungicides
physiological function
the autoimmunity phenotypes in mpk4, mekk1, and mkk1 mkk2 mutant plants are caused by activation of defense responses mediated by SUMM1
physiological function
the FRK1 mitogen-activated protein kinase kinase kinase (MAPKKK) from Solanum chacoense is involved in embryo sac and pollen development, the enzyme is involved in a signalling cascade that regulates both male and female gamete development
physiological function
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the MAPKKK genes are involved in various signaling pathways
physiological function
the mitogen-activated protein kinase kinase kinase MEKK1 acts as a tristetraprolin (TTP) kinase that, together with the TNF receptor-associated factor 2 (TRAF2), constitutes not only a main determinate of the NF-kappaB-JNK cross-talk but also facilitates TTP hypermodification: MEKK1 triggers TTP phosphorylation as prerequisite for its Lys63-linked, TRAF2-mediated ubiquitination. Consequently, TTP no longer affects NF-kappaB activity but promotes the activation of JNK. MEKK1 can counteract TTP inhibition of p65-induced NF-kappaB promoter activity
physiological function
MLK4 activates NF-kB signaling by direct phosphorylation of IKKalpha. MLK4 binds and phosphorylates the NF-kappaB regulator IKKa, leading to activation of NF-kappaB signaling in glioma stem cells. MLK4 expression is inversely correlated with patient prognosis in mesenchymal gliomas, but not proneural high-grade glioblastomas. MLK4 is an upstream regulator of NF-kappaB signaling and a potential molecular target for the mesenchymal subtype of glioblastomas. IKKalpha is a direct molecular target of MLK4 that drives the NF-kappaB pathway activation, thereby promoting mesenchymal transdifferentiation of glioma stem cells. MLK4 promotes radioresistance in glioblastoma. MLK4 is the only gene that is required for survival of mesenchymal, but not proneural, glioma spheres
physiological function
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RAF kinases exhibit high substrate selectivity, exclusively targeting the dual-specificity (Tyr/Thr) kinases MEK1/2. Regulation of RAF kinases is extremely complex and strictly controlled by several factors and events, including protein-protein interactions, phosphorylation/dephosphorylation at numerous sites, and oligomerization state
physiological function
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isoform MAP3K8 mediates the LH-induced stimulation of progesterone synthesis through the protein kinase A/mitogen-activated protein kinase signalling pathway in porcine corpus lutem
physiological function
isoform MAP4K3 positively regulates preterm skeletal muscle satellite cell myogenesis, but may not regulate mTORC1 activity. Isoform MAP4K3 may play a role in target of rapamycin complex 1 full activation in response to leucine
physiological function
isoform MEKK4 is involved in innate immune response of blood clam
physiological function
isoform MKKK20 participates in the osmotic stress response through its regulation of MPK6
physiological function
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isoform MKKK7 negatively regulates flagellin-triggered signalling and basal immunity in Arabidopsis. Isoform MKKK7 attenuates MPK6 activity and defense gene expression. Moreover, MKKK7 suppresses the reactive oxygen species burst downstream of flagellin receptor FLS2
physiological function
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mitogen-activated protein kinase kinase kinase FRK2 is involved in early embryo sac development in Solanum chacoense. Overexpression lines lead to a drastic decrease in seed numbers, presumably caused by a conversion of the ovule into a carpel-like structure
physiological function
MKKK20 autophosphorylates and phosphorylates both mitogen-activated protein kinase kinase MKK3 and MPK18. When all three kinases are combined, no synergistic effect is observed on MPK18 phosphorylation. MKKK20 acts upstream of MPK18 and MKK3. MKKK20 and MKK3 mutants are sensitive to microtubule-disrupting drugs
physiological function
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RAF22 and RAF28 are involved in the regulation of embryogenesis
physiological function
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the enzyme is required for hyphal growth and virulence in Aspergillus flavus. The enzyme is important for conidia and sclerotia formation, maintains cell wall integrity, and plays a negative role in the regulation of oxidative response
physiological function
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transgenic plants overexpressing a truncated enzyme of MAPKKK5 show increased plant height, grain length, grain width, 1000-grain weight, grain number per main panicle, and yield. The enzyme positively regulates plant height and yield in rice by affecting cell size
physiological function
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mitogen-activated protein (MAP) kinase cascades are universal signaling modules in eukaryotes, which relay external or internal upstream signals to downstream targets. Arabidopsis thaliana putative MAP kinase kinase kinases Raf10 and Raf11 are positive regulators of seed dormancy. Raf11 plays a redundant role in abscisic acid response
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physiological function
-
mitogen-activated protein (MAP) kinase cascades are universal signaling modules in eukaryotes, which relay external or internal upstream signals to downstream targets. Arabidopsis thaliana putative MAP kinase kinase kinases Raf10 and Raf11 are positive regulators of seed dormancy and abscisic acid response
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physiological function
-
the autoimmunity phenotypes in mpk4, mekk1, and mkk1 mkk2 mutant plants are caused by activation of defense responses mediated by SUMM1
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physiological function
-
MEKK1 is involved in negative regulation of cell death and immunity
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physiological function
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mitogen-activated protein kinase kinase kinase BcOs4 is required for vegetative differentiation and pathogenicity in Botrytis cinerea. BcOS4 is involved in vegetative differentiation, virulence, adaption to hyperosmotic and oxidative stresses, and to fungicides
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additional information
MEKK1 has a kinase domain at its C-terminus, and a PHD domain at its N-terminus responsible for its E3 ligase activity. The PHD domain of MEKK1 mediates not only its Lys63-linked autoubiquitination, leading to a stabilized interaction with other proteins, but also ERK1/2 polyubiquitination and degradation in response to stress stimuli
additional information
structural insights into the molecular recognition between cerebral cavernous malformation 2 (CCM2) and mitogen-activated protein kinase kinase kinase 3 (MEKK3): CCM2 functions as an adaptor protein that mediates the activation of MEKK3 signaling in response to osmotic stress, or negatively regulates MEKK3 signaling, which is important for normal cardiovascular development. CCM2ct assembles into a global six-helix domain by intramolecular interaction, CCM2ct intramolecular interaction is weak. The N-terminal amphiphilic helix of MEKK3 (MEKK3-n_helix) as the essential structural element for CCM2ct binding, CCM2ct directly interacts with MEKK3 N-terminal helix. The binding of CCM2ct to MEKK3-n_helix resembles CCM2ct intramolecular interaction, surface plasmon resonance, analysis, overview. Determinative roles of MEKK3 residues Leu7, Ile10, Leu14, and Leu17 and auxiliary role for residue Glu3 in CCM2ct-MEKK3 recognition by mutational analysis. The resulting CCM2-MEKK3 interaction builds a molecular platform for regulating MEKK3 signaling
additional information
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NMR structure analysis of RAS-binding domain (RBD) from human B-RAF kinase, and analysis of the complex between B-RAF RBD and the GppNHp bound form of HRAS in solution, overview. B-Raf CR1 region is composed of a RAS-binding domain (RBD) immediately followed by a cysteine-rich domain, which can bind two zinc ions. CR1 interacts with RAS and membrane phospholipids. Region CR2 is a serine/threonine-rich domain containing a 14-3-3 binding site, and region CR3 features the kinase domain. RAS and BRAF binding structure analysis, detailed overview. Allosteric conformational changes upon RAS binding, propagated through the beta-sheet and alpha-helical core of the protein domain
Show AA Sequence and Transmembrane Helices (10003 entries)
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
180000
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
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dimerization through the catalytic domain is essential for MEKK2 activation, the dimerization motif is in the catalytic domain, the N-terminal domain is not required for dimerization, overview
additional information
additional information
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domain and motif analysis of Brachypodium distachyon MAPKKKs, overview
additional information
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COT30-467 forms very tightly bound complexes with p105DELTAN which remain intact at 2-4 M urea
additional information
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the MLTKalpha C-terminus possesses an alpha-motif in vicinity to the leucine zipper, the alpha-motif is supposed to be a regulatory and phosphorylation site
additional information
MEKK1 has a kinase domain at its C-terminus, and a PHD domain at its N-terminus responsible for its E3 ligase activity
additional information
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MEKK1 forms complexes with FAK involved in regulation of cell migration, overview
additional information
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subdomain VIII is a specificity-determining region in MEKK1
additional information
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the C-terminus contains the kinase domain, two ubiquitin interaction motifs, a region of interaction with small GTPases, and a caspase 3-like cleavage site
additional information
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the subdomain X is required for phosphorylation and activation of MAPKKs in vivo
additional information
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the large enzyme possesses several domains including a proline-rich region, indispensable for activity, and a 60-amino acid-long polyglutamine stretch, which is not necessary for full activity
additional information
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structural analysis of the sterile alpha motif, SAM, domain of Ste11 MAPKKK and of Ste50 effector, several hydrophobic secondary structures and amino acids are required for effective binding, overview
additional information
a short C-terminal region of 42 amino acids (position 282--323) follows kinase subdomain XI, presence of a cluster of two short basic amino acid sequences predicted to form a bipartite nucleoplasmin-type nuclear localization sequence (NLS)
additional information
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a short C-terminal region of 42 amino acids (position 282--323) follows kinase subdomain XI, presence of a cluster of two short basic amino acid sequences predicted to form a bipartite nucleoplasmin-type nuclear localization sequence (NLS)
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
proteolytic modification
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cleavage by caspase-3 at a specific C-terminal cleavage site generates a 91 kDa, catalytically active enzyme fragment
ubiquitination
the PHD domain of MEKK1 mediates its Lys63-linked autoubiquitination, leading to a stabilized interaction with other proteins. Autoubiquitination of MEKK1 strongly depends on its kinase activity, as well as the presence of TRAF2
additional information
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the active MEKK1 stimulates its own ubiquitinylation in vivo which has a negatively regulating function
phosphoprotein
MAP kinase kinase kinase MEKK2 interacts with MPK4 and is phosphorylated by MPK4 in vitro
phosphoprotein
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MAP kinase kinase kinase MEKK2 interacts with MPK4 and is phosphorylated by MPK4 in vitro
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phosphoprotein
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MEKK2 and MEKK3 are phosphorylated at the N-terminus and thereby activated by kinase WNK1, residues K385 and K391, respectively, are involved
phosphoprotein
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MLTKalpha is phosphorylated by PKNalpha, probably at the C-terminal alpha-motif
phosphoprotein
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phosphorylation at Ser526 and Thr530 in the activation loop is required for MEKK3 activation, dephosphorylation is blocked by binding to protein 14-3-3
phosphoprotein
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MEKK2 and MEKK3 are activated by phosphorylation, determination of phosphorylation sites, S519 is a key regulator phosphorylation site in MEKK2, other sites are Thr521 and Thr523
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
10 mg/ml TAK1-TAB1 by hanging-drop method at 20°C, mixing of 0.004 ml of protein solution with 0004 ml of reservoir solution containing 0.65-0.75 M sodium citrate, 0.2 M NaCl, 0.1 M Tris, pH 7.0, and 5 mM adenosine, X-ray diffraction structure determination and analysis, molecular replacement with inactive TAK1-TAB1 structure, PDB cID 2YIY, as search model
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purified recombinant RAS-binding domain (RBD) from human B-RAF kinase, by microbatch-under-oil crystallization method at 18°C, X-ray diffraction structure determination and analysis at 2.0 A resolution
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
K361M
P740L
D13A
site-directed mutagenesis, the mutation of the conserved Asp13 of MEKK3 to Ala completely abolishes the binding between CCM2ct and MEKK3nt
D169A
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site-directed mutagenesis, the kinase-dead mutation of TAO2-1 does not influence the ERK5 activation level
E1372Q
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site-directed mutagenesis, the MTK1 mutant shows altered substrate specificity comapred to the wild-type enzyme
E3A
site-directed mutagenesis, the mutation of the nonconserved Glu3 of MEKK3 to Ala causes a 2fold reduction of the binding affinity between CCM2ct and MEKK3nt
I10D
site-directed mutagenesis, the mutation completely abolishes the binding between CCM2ct and MEKK3nt
K1371D
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site-directed mutagenesis, MTK1 mutant catalytic site mutant, inactive mutant, no interaction with substrate MKK6 docking site mutants
K1371E
-
site-directed mutagenesis, MTK1 mutant catalytic site mutant, inactive mutant, no interaction with substrate MKK6 docking site mutants
K1371G
-
site-directed mutagenesis, MTK1 mutant catalytic site mutant, inactive mutant, no interaction with substrate MKK6 docking site mutants
K1371R
-
site-directed mutagenesis, MTK1 mutant catalytic site mutant, inactive mutant, no interaction with substrate MKK6 docking site mutants
K14D
site-directed mutagenesis, the mutation completely abolishes the binding between CCM2ct and MEKK3nt
K17D
site-directed mutagenesis, the mutation completely abolishes the binding between CCM2ct and MEKK3nt
K391A
-
site-directed mutagenesis of MEKK3, the mutant shows highly reduced activity compared to the wild-type enzyme
K7D
site-directed mutagenesis, the mutation completely abolishes the binding between CCM2ct and MEKK3nt
K7R
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sustains the strong binding affinity, Kd is 0.37 micromol, dilution is exothermal like with wild-type
Q1254E
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site-directed mutagenesis, the MEKK1 mutant shows altered substrate specificity comapred to the wild-type enzyme
R14A
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binds to MEK5 PB1 with binding affinity of Kd 0.5 micromol, comparable to that of wild-type, dilution is endothermal
R5A
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binding affinity decreases greatly to 1.6 micromol, dilution is endothermal
R76A
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binds to MEK5 PB1 with binding affinity of Kd 0.22 micromol comparable to that of wild-type, dilution is endothermal
S526A
-
site-directed mutagenesis of MEKK3, the mutant shows highly reduced activity compared to the wild-type enzyme
S526D
-
site-directed mutagenesis of MEKK3, the mutant shows reduced activity compared to the wild-type enzyme
S526E
-
site-directed mutagenesis of MEKK3, the mutant shows reduced activity compared to the wild-type enzyme
T516A/S520A
MEKK3 with double alanine mutations can not bind the catalytic subunit of protein phosphatase 2a
T516E/S520D
double mutant, MEKK3 is phosphorylated at Thr-516 and Ser-520 within the kinase activation loop by protein phosphatase 2a
T530A
-
site-directed mutagenesis of MEKK3, the mutant shows highly reduced activity compared to the wild-type enzyme
T530D
-
site-directed mutagenesis of MEKK3, the mutant shows highly reduced activity compared to the wild-type enzyme
T530E
-
site-directed mutagenesis of MEKK3, the mutant shows highly reduced activity compared to the wild-type enzyme
V599E
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naturally occurring mutation of cancer cells, the mutation leads to 10fold increased enzyme activity compared to the wild-type enzyme, and constitutive, Ras-independent activation, siRNA-mediated depletion of the mutant enzyme diminishes the enzyme activity and also cell proliferation
C441A
-
site-directed mutagenesis, the mutant enzyme is not ubiquitinylated and thus shows a higher ERK activating activity
F1443A
I1394/L1402A
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site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
I1445A
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site-directed mutagenesis of MEKK1, the mutation has a deleterious effect on MEKK1 function
I1454A
-
site-directed mutagenesis of MEKK1, the mutation abolishes the in vitro interaction with MKK4, but retains the in vivo activity
L1402A/F1443A
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site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
L1458A
-
site-directed mutagenesis of MEKK1, the mutation has a deleterious effect on MEKK1 function
P1452A
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site-directed mutagenesis of MEKK1, the mutation has a deleterious effect on MEKK1 function
P1455A
-
site-directed mutagenesis of MEKK1, the mutation has a deleterious effect on MEKK1 function
P580A
-
site-directed mutagenesis of MEKK2, the mutant shows 82% of wild-type activity
P584A
-
site-directed mutagenesis of MEKK2, the mutant shows activity similar to the wild-type enzyme
Q1405R/Q1406R
-
site-directed mutagenesis C-terminal to the subdomain VIII, creation of an optimal recognition site for protease furin, the mutant binds MKK4 more tightly than the wild-type enzyme, MKK4 binding protects the mutant enzyme from proteolytic cleavage
S1459A
-
site-directed mutagenesis of MEKK1, the mutation abolishes the in vitro interaction with MKK4, but retains the in vivo activity
S519A
-
site-directed mutagenesis, MEKK2 phosphorylation site mutant, inactive mutant
S526A
-
site-directed mutagenesis, MEKK3 phosphorylation site mutant, inactive mutant
T521A
-
site-directed mutagenesis, MEKK2 phosphorylation site mutant, the mutant shows slightly reduced activity compared to the wild-type enzyme
T523A
-
site-directed mutagenesis, MEKK2 phosphorylation site mutant, the mutant shows slightly reduced activity compared to the wild-type enzyme
V586A
-
site-directed mutagenesis of MEKK2, the mutant shows activity similar to the wild-type enzyme
DELTA381-400
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defective in osmotic induction of the 8xCRE-lacZ reporter, mutant is osmosensitive
DELTA401-420
-
defective in osmotic induction of the 8xCRE-lacZ reporter, mutant is osmosensitive
DELTA421-440
-
defective in osmotic induction of the 8xCRE-lacZ reporter, mutant is osmosensitive
L72R
-
site-directed mutagenesis, highly increased tight binding of Ste50 wild-type compared to the Ste11 wild-type enzyme
K391M
-
catalytically inactive mutant of MEKK3, is not phosphorylated at Ser526, abrogates NF-kappaB luciferase activity
S526A
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fails to activate the NF-kappaB luciferase reporter gene and is unable to activate the MEK and ERK pathway
S526D
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is capable of activating a NF-kappaB luciferase reporter gene as well as ERK and MEK
S526E
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is capable of activating a NF-kappaB luciferase reporter gene as well as ERK and MEK
T530A
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fails to activate the NF-kappaB luciferase reporter gene and is unable to activate the MEK and ERK pathway
additional information
K361M
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kinase-inactive MEKK1, rescues the mekk1 dwarf penotype. Elevated temperature dramatically improves the growth of mekk1 plants. K361M plants are fully fertile and grow with a morphology closely resembling wild-type plants. When treated with pathogenic bacteria, K361M plants are slightly more susceptible to an avirulent strain of Pseudomonas syringae and show a delayed hypersensitive response
K361M
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mutation of the kinase domain of MEKK1 reduces the relative expression of the WRKY53 promoter driven GUS gene from 200% in the presence of intact MEKK1 to 132% in the presence of the mutated form
F1443A
-
site-directed mutagenesis of MEKK1, the mutation abolishes the in vitro interaction with MKK4, but retains the in vivo activity
F1443A
-
site-directed mutagenesis, subdomain X mutation, the mutant shows reduced activity compared to the wild-type enzyme
additional information
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YODA null mutation leads to excess stomata, whereas constittive activation of YODA eliminated stomata
additional information
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mekk1 knockout mutants, display a severe dwarf phenotype, constitutive callose deposition, and constitutive expression of pathogen response genes. The dwarf phenotype is largely rescued by introduction into mekk1 knockout plants of either mutant K361M or a nahG transgene that degrades salicylic acid
additional information
mekk1-1 and mekk1-2 mutants, exhibit dwarfism and lethality, and also showed early senescence in cotyledons, loss of MEKK1 results in tissue-specific cell death, tissue-specific H2O2 accumulation and constitutive defense responses. Little or no suppression of dwarfism in mekk1/edm1 or mekk1/rar1 double mutants compared with mekk1 when grown at 22°C, but dwarf phenotype is highly recovered in mekk1/rar1 at 26°C, whereas mekk1/edm1 plants are only slightly bigger than mekk1. In mekk1/sid2 mutants growth defect, cell death, H2O2 accumulation and callose deposition phenotypes are not suppressed at 22°C. However, similar to rar1, sid2 partially suppresses these mekk1 phenotypes at 26°C, although the suppression effect is not as strong as in rar1
additional information
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MEKK1-deficient plants, are misregulated in the expression of a number of genes involved in cellular redox control and accumulate reactive oxygen species. Homozygous mekk1 mutant plants exhibit a lethal phenotype when developing true leaves. Mutant plants stay dwarfed and never reach maturity to produce seeds. Mekk1 and mpk4 mutant plants show similarities with respect to both, phenotype and H2O2 accumulation
additional information
generation of summ1 mutants and of summ1-1 mkk1 mkk2 and summ1-2 mkk1 mkk2 triple mutants. To map the summ1-1 mutation, summ1-1 mkk1 mkk2 (in the Columbia background) is crossed with Landsberg erecta (Ler). F2 plants homozygous for mkk1 mkk2 are selected forlinkage analysis. Crude mapping using 48 such plants reveals that summ1-1 is flanked by markers T13D4 and T15F16 on chromosome 4. Constitutive expression of defense marker genes PR1 and PR2 is completely suppressed in the summ1-1 mkk1 mkk2 and summ1-2 mkk1 mkk2 triple mutants. Suppression of mkk1 mkk2 mutant phenotypes by summ1-1 and summ1-2, overview. Mutants summ1-1 mkk1 mkk2 and summ1-2 mkk1 mkk2 exhibit wild type-like morphology
additional information
generation of summ1 mutants and of summ1-1 mkk1 mkk2 and summ1-2 mkk1 mkk2 triple mutants. To map the summ1-1 mutation, summ1-1 mkk1 mkk2 (in the Columbia background) is crossed with Landsberg erecta (Ler). F2 plants homozygous for mkk1 mkk2 are selected forlinkage analysis. Crude mapping using 48 such plants reveals that summ1-1 is flanked by markers T13D4 and T15F16 on chromosome 4. Constitutive expression of defense marker genes PR1 and PR2 is completely suppressed in the summ1-1 mkk1 mkk2 and summ1-2 mkk1 mkk2 triple mutants. Suppression of mkk1 mkk2 mutant phenotypes by summ1-1 and summ1-2, overview. Mutants summ1-1 mkk1 mkk2 and summ1-2 mkk1 mkk2 exhibit wild type-like morphology
additional information
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generation of summ1 mutants and of summ1-1 mkk1 mkk2 and summ1-2 mkk1 mkk2 triple mutants. To map the summ1-1 mutation, summ1-1 mkk1 mkk2 (in the Columbia background) is crossed with Landsberg erecta (Ler). F2 plants homozygous for mkk1 mkk2 are selected forlinkage analysis. Crude mapping using 48 such plants reveals that summ1-1 is flanked by markers T13D4 and T15F16 on chromosome 4. Constitutive expression of defense marker genes PR1 and PR2 is completely suppressed in the summ1-1 mkk1 mkk2 and summ1-2 mkk1 mkk2 triple mutants. Suppression of mkk1 mkk2 mutant phenotypes by summ1-1 and summ1-2, overview. Mutants summ1-1 mkk1 mkk2 and summ1-2 mkk1 mkk2 exhibit wild type-like morphology
additional information
identification of a Raf11 knockout mutant, raf11 (SALK_047070), the T-DNA is located in the ninth exon of the Raf11 gene, and Raf11 expression is abolished completely. Contruction of a Raf10 and Raf11 double knockout mutant line, ais143 raf11, by crossing ais143 with raf11, phenotypes, overview
additional information
identification of a Raf11 knockout mutant, raf11 (SALK_047070), the T-DNA is located in the ninth exon of the Raf11 gene, and Raf11 expression is abolished completely. Contruction of a Raf10 and Raf11 double knockout mutant line, ais143 raf11, by crossing ais143 with raf11, phenotypes, overview
additional information
isolation of the abscisic acid-insensitive mutant, ais143, by activation tagging screen. The T-DNA is located in one of the exons (8/13) of the coding region of putative mitogen-activated protein (MAP) kinase kinase kinase (MAP3K) gene, Raf10, thereby abolishing its expression in the mutant. ais143 exhibits reduced seed dormancy as well as reduced abscisic acid sensitivity. The phenotypes are complemented by the wild-type Raf10 gene, and the overexpression of Raf10 results in delayed seed germination and enhanced the abscisic acid sensitivity
additional information
isolation of the abscisic acid-insensitive mutant, ais143, by activation tagging screen. The T-DNA is located in one of the exons (8/13) of the coding region of putative mitogen-activated protein (MAP) kinase kinase kinase (MAP3K) gene, Raf10, thereby abolishing its expression in the mutant. ais143 exhibits reduced seed dormancy as well as reduced abscisic acid sensitivity. The phenotypes are complemented by the wild-type Raf10 gene, and the overexpression of Raf10 results in delayed seed germination and enhanced the abscisic acid sensitivity
additional information
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identification of a Raf11 knockout mutant, raf11 (SALK_047070), the T-DNA is located in the ninth exon of the Raf11 gene, and Raf11 expression is abolished completely. Contruction of a Raf10 and Raf11 double knockout mutant line, ais143 raf11, by crossing ais143 with raf11, phenotypes, overview
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additional information
-
isolation of the abscisic acid-insensitive mutant, ais143, by activation tagging screen. The T-DNA is located in one of the exons (8/13) of the coding region of putative mitogen-activated protein (MAP) kinase kinase kinase (MAP3K) gene, Raf10, thereby abolishing its expression in the mutant. ais143 exhibits reduced seed dormancy as well as reduced abscisic acid sensitivity. The phenotypes are complemented by the wild-type Raf10 gene, and the overexpression of Raf10 results in delayed seed germination and enhanced the abscisic acid sensitivity
-
additional information
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generation of summ1 mutants and of summ1-1 mkk1 mkk2 and summ1-2 mkk1 mkk2 triple mutants. To map the summ1-1 mutation, summ1-1 mkk1 mkk2 (in the Columbia background) is crossed with Landsberg erecta (Ler). F2 plants homozygous for mkk1 mkk2 are selected forlinkage analysis. Crude mapping using 48 such plants reveals that summ1-1 is flanked by markers T13D4 and T15F16 on chromosome 4. Constitutive expression of defense marker genes PR1 and PR2 is completely suppressed in the summ1-1 mkk1 mkk2 and summ1-2 mkk1 mkk2 triple mutants. Suppression of mkk1 mkk2 mutant phenotypes by summ1-1 and summ1-2, overview. Mutants summ1-1 mkk1 mkk2 and summ1-2 mkk1 mkk2 exhibit wild type-like morphology
-
additional information
construction and complementation of the BcOS4 deletion mutant. Comparison of mycelial growth rate of the wild-type strain 38B1, the BcOS4 deletion mutant DELTABcOs4-E8, and the complemented strain DELTABcOs4-E8-C23 on potato dextrose agar and minimal medium, overview The BcOS4 deletion mutant is significantly impaired in vegetative growth and conidial formation. All the defects are restored by genetic complementation of the BcOS4 deletion mutant with the wild-type BcOS4 gene. Phenotype of the BcOS4 deletion mutant, overview. The mutant strain exhibits increased sensitivity to the dicarboximide fungicide iprodione and the phenylpyrrole fungicide fludioxonil
additional information
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construction and complementation of the BcOS4 deletion mutant. Comparison of mycelial growth rate of the wild-type strain 38B1, the BcOS4 deletion mutant DELTABcOs4-E8, and the complemented strain DELTABcOs4-E8-C23 on potato dextrose agar and minimal medium, overview The BcOS4 deletion mutant is significantly impaired in vegetative growth and conidial formation. All the defects are restored by genetic complementation of the BcOS4 deletion mutant with the wild-type BcOS4 gene. Phenotype of the BcOS4 deletion mutant, overview. The mutant strain exhibits increased sensitivity to the dicarboximide fungicide iprodione and the phenylpyrrole fungicide fludioxonil
additional information
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construction and complementation of the BcOS4 deletion mutant. Comparison of mycelial growth rate of the wild-type strain 38B1, the BcOS4 deletion mutant DELTABcOs4-E8, and the complemented strain DELTABcOs4-E8-C23 on potato dextrose agar and minimal medium, overview The BcOS4 deletion mutant is significantly impaired in vegetative growth and conidial formation. All the defects are restored by genetic complementation of the BcOS4 deletion mutant with the wild-type BcOS4 gene. Phenotype of the BcOS4 deletion mutant, overview. The mutant strain exhibits increased sensitivity to the dicarboximide fungicide iprodione and the phenylpyrrole fungicide fludioxonil
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additional information
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construction of a kinase-defective MTLKalpha mutant, expression of a kinase-defective PKNalpha mutant results in inhibition of MLTKalpha activity and p38 kinase induction
additional information
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MEKK3 overexpression confers resistance to apoptosis through activation of NF-kappaB
additional information
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overexpression of DLK in cultured keratinocytes results in altered features of the cell concerning suprabasal localization, cell shape, compacted cytoplasm, DNA fragmentation, and regulation of filaggrin expression, which is upregulated, terminally differentiated phenotype, the transglutaminase activity is increased leading to cornified cell envelope formation, overview
additional information
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overexpression of WNK1 in HEK293 cells leads to increased enzyme activity, a kinase-dead mutation of MEKK1 does not influence the ERK5 activation level
additional information
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the BRAF gene is mutated in several cancers, especially in cutaneous melanoma
additional information
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deletion of the CRIB domain of MEKK4 diminishes but does not abolish Cdc42 binding
additional information
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MEKK1 knockdown in invasive human breast carcinoma cells leads to reduced uPA expression, cell migration, and invasiveness
additional information
lentiviral, shRNA-mediated MEKK1 knockdown in HUVEC. Generation of a dominant negative MEKK1 mutant
additional information
MLK4 silencing with the short hairpin RNA (shRNA) technique
additional information
an OMTK1 mutant reduced in MMK3 complex formation shows decreased MMK3 and cell death activation
additional information
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mutations in the MEKK subdomain X differentially affect MEKK2 and MEKK1 activity, overview
additional information
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ASK1-/- cells, are resistant to TNF-induced apoptosis, produce low levels of TNF after LPS injection and are resistant to LPS-induced septic shock. In macrophages from TPL-2 deficient mice, activation of ERK is blocked following TLR4, TLR2 or TNFR1 stimulation, whereas activation of p38 and JNK via these receptors is unaffected, LPS upregulation of TNF is reduced, are resistant to endotoxin shock induced by LPS and D-galactosamine. TAK1-/- mice die early in uterus. Mlk3-/- mice are viable. In Mekk1-/- mice, normal or blocked JNK activation induced by TNF and IL-1, discrepancy in two different studies. MEKK3-deficient mice, embryonic lethal, activation of JNK and p38 is blocked, but not of ERK by IL-1 and TLR4
additional information
endogenous ASK2 constitutively degraded in ASK1-deficient cells, kinase-negative mutant of ASK1 effectively activates MAP2K and is more competent to respond to oxidative stress than ASK2 alone. Knockdown of ASK2 reveals that ASK2 is required for oxidative stress-induced JNK activation
additional information
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Gckr-/- cells, have a significant defect in Wnt-mediated JNK activation and in induction of beta-catenin compared to wild-type
additional information
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kinase inactive form of MEKK4, attenuates mesenchyme production
additional information
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MEKK1-4 knockout mice, MEKK3 knockout is embryo-lethal, displaying inadequate fetal-maternal vascularization. MEKK4 knockout is largely perinatal lethal, and associated with defective neural tube closure, shows loss of JNK and p38 activation. MEKK1-2 knockouts are associated with impaired tissue remodeling associated with wound healing and homeostasis, expression of JunB and Fra-2 is markedly increased in MEKK1-deficient mouse fibroblasts. MLK3-deficient mice are viable and fertile with only a mild defect in the epidermal tissue of the dorsal midline. Mouse embryos deficient in either B-Raf or C-Raf die before day E12.5. A-Raf deficient mice die perinatally at 1-3 weeks of age. Tpl2-deficient mice are viable and appear indistinguishable from littermates, produce reduced levels of TNFalpha in response to LPS injection, are resistant to LPS/D-galactosamine-induced pathology. TAK1-deficient mouse embryo fibroblasts show decreased IL-1beta-induced IL-6 expression, TAK1-deficient keratinocytes develop a severe postnatal inflammation, loss of MEKK1 does not alter the course of tumorigenesis or inhibit primary tumor growth, intimal hyperplasia is significantly reduced
additional information
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Mekk1deltaKD/deltaKD mice, MEKK1 ablation significantly delays skin wound closure and impairs activation of Jun NH2-terminal kinases, induction of plasminogen activator inhibitor 1, and restoration of cell-cell junctions of the wounded epidermis. Reconstituting MEKK1 expression with MEKK1 wild-type expression significantly accelerates wound closure
additional information
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MEKK4-/- mice, protein is not essential for embryonic survival, but more than 80% of mice exhibit neural tube defects and die shortly after birth. Reduced level of IFN-gamma production in response to cytokine treatment. MEKK4-3R mutant, completely abolishes CIN85 interaction and is defective in activating the p38 pathway. Intermediate MKK6 causes reduction in p38 activation in response to both oxidative stress and epidermal growth factor stimulation, less prone to ubiquitination
additional information
generation of RhoA deletions in Map3k1 wild-type, heterozygous, and knockout genetic backgrounds
additional information
ZPK/DLK-deficient mice are derived from the gene-trap embryonic stem cell clone RRN366
additional information
-
Gckr-/- cells, have a significant defect in Wnt-mediated JNK activation and in induction of beta-catenin compared to wild-type
-
additional information
construction of mutant plants for identification of genes and pathway functioning in hypersensitive response and resistance by MAPKKKalpha silencing, co-expression of tomato resistance R gene Cf9 and the Cladosporium fulvum avirulence gene avr9, a multicomponent transgenic construct, overexpression of the full length Lycopersicon esculentum enzyme or the isolated tomato enzyme kinase domain in leaves leads to pathogen-independent cell death induction, overview
additional information
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the Oryza sativa mutant, increased leaf angle1 (ila1), results from a T-DNA insertion in a group C MAPKKK gene. The increased leaf angle in ila1 is caused by abnormal vascular bundle formation and cell wall composition in the leaf lamina joint, as distinct from the mechanism observed in brassinosteroid-related mutants, phenotype, overview. ILA1 is a functional kinase with Ser/Thr kinase activity
additional information
-
enzyme-defective mutant strains AS4-44 and AS6-5 are impaired in the development of crippled growth after infection causing a cell degenerative process, and are defective in mycelium pigmentation, aerial hyphae differentiation, and making of fruiting bodies showing female sterility, construction of mutants lacking the proline-riche region or the polyglutamine stretch, mutant phenotypes, overview
additional information
-
inhibition of heterodimeric association of Ste11 and Ste50 in yeast strains leads to defects in mating and activation of high-osmolarity growth pathways
additional information
-
ssk2delta/ssk22delta/ste11delta strain, complementation of the osmo-sensitive phenotype, deletion of the LD domain of Ssk2p results in a serious localization defect when yeast cells are exposed to osmotic stress as well as an inability to facilitate the actin specific functions of Ssk2p
additional information
generation of DELTAwis4/wak1/wik1 single and DELTAwis4/wak1/wik1/DELTAwin1 double knockout mutants
additional information
generation of DELTAwis4/wak1/wik1 single and DELTAwis4/wak1/wik1/DELTAwin1 double knockout mutants
additional information
-
generation of DELTAwis4/wak1/wik1 single and DELTAwis4/wak1/wik1/DELTAwin1 double knockout mutants
additional information
-
generation of DELTAwis4/wak1/wik1 single and DELTAwis4/wak1/wik1/DELTAwin1 double knockout mutants
-
additional information
FRK2-S2, FRK2-S17, FRK2-S5, FRK2-S7, FRK2-S9, and FRK2-11 mutant sense lines reveal that overexpression of FRK2 produces smaller than normal fruits containing fewer seeds, FRK2-S2 and FRK2-S17 mutant sense lines reveal that overexpression of FRK2 leads to transformation of ovules into carpelloid structures, FRK2-S20 mutant sense line shows complete co-suppression for FRK2, plants containing the antisense construct show reduced ScFRK2 mRNA levels compared with the wild-type
additional information
FRK2-S2, FRK2-S17, FRK2-S5, FRK2-S7, FRK2-S9, and FRK2-11 mutant sense lines reveal that overexpression of FRK2 produces smaller than normal fruits containing fewer seeds, FRK2-S2 and FRK2-S17 mutant sense lines reveal that overexpression of FRK2 leads to transformation of ovules into carpelloid structures, FRK2-S20 mutant sense line shows complete co-suppression for FRK2, plants containing the antisense construct show reduced ScFRK2 mRNA levels compared with the wild-type
additional information
-
FRK2-S2, FRK2-S17, FRK2-S5, FRK2-S7, FRK2-S9, and FRK2-11 mutant sense lines reveal that overexpression of FRK2 produces smaller than normal fruits containing fewer seeds, FRK2-S2 and FRK2-S17 mutant sense lines reveal that overexpression of FRK2 leads to transformation of ovules into carpelloid structures, FRK2-S20 mutant sense line shows complete co-suppression for FRK2, plants containing the antisense construct show reduced ScFRK2 mRNA levels compared with the wild-type
additional information
construction of the ScFRK1DELTA1 or ScFRK1DELTA1DELTA2 mutants that are localized in the cytoplasm in contrast to the wild-type. Mutant phenotypes, overview
additional information
-
construction of the ScFRK1DELTA1 or ScFRK1DELTA1DELTA2 mutants that are localized in the cytoplasm in contrast to the wild-type. Mutant phenotypes, overview
additional information
overexpression of the full length enzyme or the isolated tomato enzyme kinase domain in Nicotiana benthiana leaves leads to pathogen-independent cell death induction, overview
additional information
-
enzyme inactivation by antisense expression method and expression of dominant negative MLK2 defective in the ATP binding site, which impairs the UV irradiation sensitivity, overview
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GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
binding of p105 increases the solubility and stability of COT, but decreases catalytic activity
-
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-80C
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
partial purification of Mos and B-Raf from egg extracts by heparin affinity chromatography and/or ion exchange chromatography, and GST-MEK1 affinity chromatography, recombinant His6-tagged B-Raf by nickel affinity chromatography
-
purification of recombinant MEKK1 and ASK1 by chitin affinity chromatography, endogenous MEKK1 by protein A affinity chromatography
-
purification of recombinant wild-type and mutant COT30-397s, free or complexed to p105DELTAN, and of p105DELTAN-complexed recombinant COT30-467 from Sf9 insect cells by anti-Flag immunoaffinity chromatography, the purification of free COT30-467 is not possible due to its extremely low expression level in absence of p105DELTAN
-
recombinant His6- and GST-tagged wild-type and mutants enzymes from Escherichia coli by affinity chromatography and gel filtration, the tags are cleaved off
-
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
amplified MEKK3 PB1 DNA fragments inserted between NdeI/XhoI sites of pET22b and wild-type MEKK3 PB1 with a C-terminal His tag expressed in Escherichia coli BL21 (DE3) cells, MEKK3 PB1 mutants expressed in Escherichia coli Rosetta cells
-
B-RAf, DNA and amino acid sequence determination and analysis, expression of His6-tagged B-Raf in bacteria, expression of His6-tagged and FLAG-tagged C-Raf in insect cells
-
bioinformatics analysis of the entire maize genome identifies 74 MAPKKK genes, sequence comparisons and phylogenetic analysis and tree, genomic structure, and chromosomal distributions and exon-intron structures of maize MAPKKK genes, real-time quantitative RT-PCR expression analysis of the MAPKKKs. ZmMAPKKK ORF lengths range from 1062 bp (ZmMAPKKK57) to 4014 bp (ZmMAPKKK14)
-
co-expression of FLAG-tagged MTK1 and wild-type and mutant HA-tagged MKK6 in COS-7 cells, direct and immunoprecipitation study
-
DNA and amino acid sequence determination and analysis, overexpression of the enzyme can complement the defective mutant and results in increase crippled growth after infection
-
DNA and amino acid sequence determination and analysis, sequence comparisons, overview
DNA and amino acid sequence determination and analysis, sequence comparisons, overview, MAPKKKalpha overexpression in leaves using the Agrobacterium tumefaciens transfection system
expressed as native and mutant FLAG-tag/HA-tag fusion protein in HEK293T cells, coexpression expreiments with TAK1
-
expression in embryos by microinjection in the two-cell stage, overexpression of MLK2 in COS-7 cells leading to a SEK1/MKK4-dependent hyperactivation of Jun N-terminal kinase
-
expression of a MEKK1 promoter-driven beta-Gal fusion protein in Mekk1deltaKD/deltaKD mice
-
expression of DLK in cultured keratinocytes using the adenovirus transfection method
-
expression of FLAG-tagged COT30-467 and COT30-397 in a stable and soluble form when co-expressed with the C-terminal part of p105, complex formation with p105 reduces the kcat value of COT30-397 but increases the expression level, expression of wild-type and mutant COT30-397s in Spodoptera frugiperda Sf9 cells using the baculovirus infection system
-
expression of FLAG-tagged MEKK3 in HEK293T and HeLa cells, co-expression of NF-kappaB
expression of GST-tagged full length MEKK2 and MEKK2 C-terminal and N-terminal fragments, i.e. of residues 1-619, 342-619, and 342-424, in COS-1 cells
-
expression of HA-tagged active MEKK2 and inactive S519A MEKK2 mutant catalytic sites, expression of wild-type and mutant full length MEKK2s and of wild-type and mutant MEKK3s
-
expression of His- or FLAG-tagged wild-type and mutant MEKK3s in HEK293 EBNA cells, co-expression of substrate GST-HA-tagged MKK6 substrate
-
expression of His6-tagged MEKK1 subdomain VIII, comprising residues 1174-1493, His6-tagged wild-type, full-length enzyme, and His6-tagged mutant enzymes F1443A, I1394/L1402A, Q1405R/Q1406R, and L1402A/F1443A in HeLa and COS-1 cells
-
expression of MEKK1 and ASK1 in CV-1 cells using a vaccinia virus transfection system
-
expression of Myc-tagged MEKK1 under the 35 S cauliflower mosaic virus promoter in Arabidopsis protoplasts
-
expression of wild-type and inactive mutant enzymes in HEK293T cells and in COS-7 cells as HA-tagged proteins
-
expression of wild-type and mutant MAP3Ks, MEKK1-4 and TAO2-1, in HEK293 cells, co-expression of ERK5 and WNK1
-
expression vector for the catalytic domain of MEKK1 expressed in a beta cell line or in primary pancreatic islets from transgenic mice
-
FLAG-MEKK3 excised from pBTM116 and ligated into the EcoRV site of pcDNA3.1, HEK293 EBNA cells transiently transfected with MEKK3, K391M, or point mutants in the pcDNA3.1 HisA plasmid HisA
-
full-length ASK2 cDNA inserted in pJG4-5, kinase-negative mutant of ASK1 inserted in pEG202. ASK1 and ASK2 constructs co-transformed along with the reporter plasmid pSH18-34 in EGY48 yeast strains, mutants transfected into HEK293 cells and MEF cells
full-length cDNA inserted into pGBKT7 vector to generate a MEKK1-GBD fusion construct, introduced into yeast strain Y187 containing the LacZ gene under the control of the GAL1 promoter, full-length MEKK1 fragments subcloned into the pQE30 expression vector to create pQE-MEKK1 encoding the 6 x His-tagged protein and expressed in Escherichia coli, full-length MEKK1 cDNA fragment with a HA-tag cloned into the pGFPc155c vector encoding the C-terminal part of the GFP protein and transformed to Agrobacterium tumefaciens strain GV3101/pMP90 and injected to Arabidopsis leaves
-
gene MAPKKK4.1, DNA and amino acid sequence determination and analysis, sequence comparison, phylogenetic tree, quantitative RT-PCR expression analysis, recombinant expression in transgenic Nicotiana benthamiana leaves under the driving of CaMV35S promoter, recombinant coexpression with substrate proteins MKK3 and MKK6 in Saccharomyces cerevisiae strain AH109 cells
gene MAPKKK4.2, DNA and amino acid sequence determination and analysis, sequence comparison, phylogenetic tree, quantitative RT-PCR expression analysis, recombinant expression in transgenic Nicotiana benthamiana leaves under the driving of CaMV35S promoter, recombinant coexpression with substrate proteins MKK3 and MKK6 in Saccharomyces cerevisiae strain AH109 cells
gene ScFRK1, DNA and amino acid sequence determination and analysis, phylogenetic analysis. for sense and antisense constructs, the GFP-tagged ScFRK1 cDNA is inserted in a modified pBin19 transformation vector with a Cauliflower mosaic virus (CaMV) 35S double enhancer promoter. Sense and antisense constructs are individually transformed in Agrobacterium tumefaciens LBA4404 by electroporation. Solanum chacoense plants are transformed by the leaf disc method. The ScFRK1-GFP fusion protein is restricted to the nuclei and co-localized with the 4',6-diamidino-2-phenylindole (DAPI) signal. Tissue expression patterns, overview
gene YDA, transcriptome analysis of seedlings with wild-type and altered YODA activity, overview
-
HEK293 cells are transfected with pMap3k1-luc together with the expression vectors for active RhoA, dominant-negative RhoA, and ROCKII and treated with TGF-alpha, inhibition of histone deacetylase with sodium butyrate or trichostatin A increases luciferase expression in pMap3k1-luc transfected HEK293 cells. Molecular mechanism of Map3k1 promoter regulation, overview
identification and genetic structure of 86 MAPKKK proteins encoded by 73 MAPKKK genes in Brachypodium distachyon, chromosomal locations, sequence analysis, and phylogenetic analysis and tree of 73 MAKKK family genes, detailed overview. Expression of splicing transcripts
-
ILA1 encodes a group C Raf-like MAPKKK with Ser/Thr kinase activity, recombinant expression of N-terminally GFP-tagged ILA1 in Oryza sativa cell protoplasts, quantitative real-time PCR expression analysis
-
into pBluescript, SF-9 insect cells infected with baculovirus expressing either MEKK4 or the kinase inactive form of MEKK4
-
MEKK1 and mutant K361M constructs introduced into Arabidopsis plants via Agrobacterium transformation
-
MEKK1 cDNA sequence amplified from the pCEP4-HAMEKK1 plasmid and ligated into baculovirus transfer vector pVL1393. Recombinant baculoviruses generated by contransfection with linear wild-type baculoviral DNA into Sf9 cells
-
MEKK1 fragments (1-132, 149-347, 149-636, 630-772, 766-1173, 766-1493, 1-719, and 565-1174) incorporated into pAS1CYH2 vector, expressed in Saccharomyces cerevisiae Y190 cells
-
MEKK2, DNA and amino acid sequence determination, expression of wild-type and mutant MEKK2 by reticulocyte lysate TnT T7 mixture, expression of wild-type and mutant MEKK2 and MEKK1 in COS-1 cells and in HeLa cells, coexpression with ERK5 in COS-1 cells
-
OMTK1, DNA and amino acid sequence determination, expression as GST-fusion protein, transient co-expression of Myc-tagged OMTK1 and HA-tagged MMK3 in Arabidopsis thaliana protoplasts, in vitro trabscription and translation of wild-type and mutant OMTK1 by reticulocyte lysate
overexpression of His6- and GST-tagged wild-type and mutants enzymes in Escherichia coli
-
overexpression of the mutant enzyme V599E in COS cells leading to 10.7fold increased activity
-
phylogenetic tree of kinases derived from the kinase core sequence, overview, overexpression as GST-fusion protein under control of the galactose-inducible GAL1 promotor in Escherichia coli, determination of 5'-end sequences
-
screening for MAPKKK genes and cloning of 28 genes, DNA and amino acid sequence determination and analysis, phylogenetic analysis, clonig of 28 genes comprising four MAPKKKs, seven ZIKs, and 17 Raf genes, overview
screening for MAPKKK genes and cloning of 28 genes, DNA and amino acid sequence determination and analysis, phylogenetic analysis, quantitative real-time reverse transcription-PCR expression analysis, transient recombinant expression of gene BnaMAPKKK18.1 as YFP- or GFP-tagged protein in Nicotiana benthamiana leaves via transfection method using Agrobacterium tumefaciens strain GV3101
screening for MAPKKK genes and cloning of 28 genes, DNA and amino acid sequence determination and analysis, phylogenetic analysis, quantitative real-time reverse transcription-PCR expression analysis, transient recombinant expression of gene BnaMAPKKK19.1 as YFP- or GFPtagged protein in Nicotiana benthamiana leaves via transfection method using Agrobacterium tumefaciens strain GV3101
stable expression of HA-tagged MEKK3 in HEK293, U373, and Hep3B cells, the expression of MEKK3 blocks the TRAIL-mediated activation of the apoptosis pathway and increases cell resistance to cytotoxic agents such as doxorubicin, daunorubicin, camptothecin, and paclitaxel, overview, TRAIL is a TNF-related apoptosis-inducing ligand
-
TAK1 expression in HEK-293 cells, Ror2-Tak1 interaction analysis by expression in the yeast two-hybrid system
transgenic plants carrying the sense or antisense construct of FRK2
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
1-aminocyclopropane-1-carboxylic acid decreases the expression of BnaMAPKKK18
after 12-24 h treatment of luteal cells with 100 ng/ml LH, isoform MAP3K8 expression is significantly upregulated
-
c-Jun expression binds in a phosphorylation-independent manner to the Map3k1 promoter and causes an increase in MAP3K1 expression. Activation of the EGF receptor leads to MAP3K1 induction. Inhibition of histone deacetylase with sodium butyrate or trichostatin A increases luciferase expression in pMap3k1-luc transfected HEK293 cells
challenge by the fungal pathogen Sclerotinia sclerotiorum and heat stress at 37°C induces the expression of BnaMAPKKK19
expression profiles of MAPKKK genes in Brachypodium upon virus, heat and drought stresses and under diurnal conditions, overview
-
jasmonic acid downregulates BnaZIK3, BnaZIK4, BnaRaf36, and BnaRaf39. 1-Aminocyclopropane-1-carboxylic acid represses BnaMAPKKK18, BnaZIK3, and BnaRaf36. Salicylic acid represses BnaZIK2, BnaRaf34, and BnaRaf36. Methyl viologen treatment downregulates the expression of BnaMAPKKK17, BnaRaf34, and BnaRaf36, while abscisic acid represses BnaZIK3 expression but exerts no effect on the transcription of the other genes. Salinity downregulates BnaMAPKKK20, BnaZIK3, BnaZIK8, and BnaRaf17, as well as BnaRaf29 and BnaRaf34. Expression of BnaZIK2, -3, -4, and BanRaf17 is decreased by heat treatment. Moderate cold stress at 4°C decreased the transcript abundance of BnaMAPKKK17, ZIK2, -3, -4, and BanRaf39. Challenge by the fungal pathogen Sclerotinia sclerotiorum represses the expression of BnaRaf28, -29, -30, and -36
jasmonic acid induces BnaRaf30. 1-Aminocyclopropane-1-carboxylic acid induces BnaZIK8 and BnaRaf29. Salicylic acid significantly induces BnaMAPKKK18 and BnaRaf28. Salinity induces BnaMAPKKK20 and BnaRaf36. Heat treatment at 37°C induces BnaMAPKKK18, -19, and BnaRaf35 Moderate cold stress at 4°C increases the transcript abundance of BnaMAPKKK20 and BnaRaf29. Challenge by the fungal pathogen Sclerotinia sclerotiorum significantly induces BnaMAPKKK19, ZIK4, Raf34, -35, and -39. Oxalic acid slightly induces BnaMAPKKK20
mixed lineage kinase 4 (MLK4) is overexpressed in mesenchymal but not proneural glioma stem cells. gene MLK4 is significantly upregulated in mesenchymal glioma spheres by 4fold or more compared with proneural spheres and/or somatic cell types including normal neural progenitors and astrocytes. MLK4 expression is enriched in the stemness-associated ALDEFLUOR-positive subpopulations in MES 83 glioma spheres
molecular mechanisms that control MAP3K1 expression, c-Jun regulates the Map3k1 promoter, overview
Raf10 expression in seedlings is induced by ABA, salt, mannitol and cold treatment
Raf11 expression in seedlings is induced by ABA, salt, mannitol and cold treatment
RhoA knockout in the ocular surface epithelium decreases MAP3K1 expression
salicylic acid and heat stress at 37°C induces the expression of BnaMAPKKK18
the MLK4 promoter is hypermethylated in proneural tumors with isocitrate dehydrogenase 1 (IDH1) mutation, suggesting that epigenetic silencing is one mechanism by which MLK4 is expressed at lower levels in proneural gliobalstomas
the mRNA expression of isoform MEKK4 is up-regulated significantly in hemocytes after infection with lipopolysaccharide (3.4fold after 24 h), Vibrio parahaemolyticus (3.2fold after 6 h) or Vibrio alginolyticus (2.5fold after 12 h)
Raf10 expression in seedlings is induced by ABA, salt, mannitol and cold treatment
Raf10 expression in seedlings is induced by ABA, salt, mannitol and cold treatment
-
-
Raf11 expression in seedlings is induced by ABA, salt, mannitol and cold treatment
Raf11 expression in seedlings is induced by ABA, salt, mannitol and cold treatment
-
-
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
medicine
additional information
analysis
-
development of a protein chip consisting of a silicone elastomer microwell array with recombinant enzyme covalently attached to the wells via a 3-glycidoxypropyltrimethoxysilane crosslinker for large scale activity assay, overview
analysis
-
proline cis-trans isomerization of MEKK3 PB1 of the Gln38-Pro39 bond, first case of structural heterogeneity within PB1 domains, major difference between both isomers in the Pro39 region. Residues Gly37-Leu40 form a type VIb beta-turn in the cis conformation, whereas no obvious character of beta-turn is observed in the trans conformation. Internal motions in the beta3/beta4-turn on a microsecond-millisecond time scale
medicine
-
cleavage of MEKK1 and caspase-3 is highly increased in adenovirus-mediated overexpression of melanoma differentiation-associated gene-7treated H1299-dnIkappaBalpha tumors than in adenovirus-mediated overexpression of melanoma differentiation-associated gene-7treated H1299-Neo tumors
medicine
-
GCKR facilitates both canonical and noncanonical Wnt signaling in B lymphocytes
medicine
-
GCKR facilitates both canonical and noncanonical Wnt signaling in B lymphocytes
medicine
-
gene amplification and corresponding increased Tpl-2 expression in some human breast cancers
medicine
-
IL-1beta through MEKK1 inhibits human insulin gene transcription and does so, at least in part, by decreasing MafA transcriptional activity at the RIPE3b control element. Since inappropriate insulin biosynthesis contributes to beta cell dysfunction, inhibition of MEKK1 may decelerate or prevent progression from a prediabetic state to diabetes mellitus
medicine
-
MEKK4 is a critical signaling molecule during cardiovascular development, plays an important role in cardiac cushion morphogenesis, kinase activity of MEKK4 is essential, but not sufficient, to support developmental epithelial to mesenchymal transformation
medicine
-
role in epithelial wound healing, transmits wound signals, leading to the transcriptional activation of genes involved in ECM homeostasis, epithelial cell migration, and wound reepithelialization
medicine
-
stress kinase MEKK1-induced MMP-1 expression in human arthritis-affected synovial cells is mediated, in large part, by c/EBPbeta (NF-kappaBp65) promoter transactivation
medicine
ZPK/DLK can become a strategic therapeutic target in motor neuron diseases in which aberrant activation of the apoptogenic cascade is involved
medicine
-
GCKR facilitates both canonical and noncanonical Wnt signaling in B lymphocytes
-
additional information
ASK2, a highly related serine/threonine kinase to ASK1, functions as a MAP3K only in a heteromeric complex with ASK1
additional information
ASK2, a highly related serine/threonine kinase to ASK1, functions as a MAP3K only in a heteromeric complex with ASK1
additional information
-
cells can customize their transcriptional response to MAPKKK cascade signaling by selective expression of the SMRT or N-CoR locus, by selective utilization of a specific corepressor splice variant, and by selective exploitation of specific tiers of the MAPK cascade
additional information
-
may play a structural role in signaling, independent of its protein kinase activity, MEKK1 kinase activity may not be required to activate FLS2-mediated defense responses in Arabidopsis. MEKK1 acts upstream of MPK4 as a negative regulator of pathogen response pathways, a function that may not require MEKK1's full kinase activity
additional information
-
MEKK1 has a dual function, it can bind to the promoter of WRKY53 and it can interact with the WRKY53 on the protein level and can phosphorylate WRKY53 in vitro thereby increasing its DNA-binding activity. MEKK1 may be able to take a very direct short cut in MAPK signalling by directly phosphorylating a transcription factor
additional information
MEKK1 negatively regulates temperature-sensitive and tissue-specific cell death and H2O2 accumulation that are partly dependent on both RAR1, a key component in resistance protein function, and SID2, an isochorismate synthase required for salicylic acid production upon pathogen infection
additional information
-
MEKK1 regulates multiple processes during vegetative development, accumulation of reactive oxygen species and redox homeostasis
additional information
role of FRK2 in pre- and post-fertilization events, overexpression of FRK2 leads to the production of fruits with a severely reduced number of seeds, and leads to changes in the expression of the class D floral homeotic gene ScFBP11, suggesting that FRK2 kinase may interact, directly or indirectly, with the FBP7/11 pathway that directs establishment of ovule identity
additional information
role of FRK2 in pre- and post-fertilization events, overexpression of FRK2 leads to the production of fruits with a severely reduced number of seeds, and leads to changes in the expression of the class D floral homeotic gene ScFBP11, suggesting that FRK2 kinase may interact, directly or indirectly, with the FBP7/11 pathway that directs establishment of ovule identity
additional information
-
role of FRK2 in pre- and post-fertilization events, overexpression of FRK2 leads to the production of fruits with a severely reduced number of seeds, and leads to changes in the expression of the class D floral homeotic gene ScFBP11, suggesting that FRK2 kinase may interact, directly or indirectly, with the FBP7/11 pathway that directs establishment of ovule identity
additional information
-
Ssk2p is one of the three MEKK kinases in the HOG pathway, the other two being Ste11p and Ssk22p, Ssk2p is homologous to MEKK4, monitors the integrity of the actin cytoskeleton and regulates its recovery from osmotic stress
additional information
-
the association between MEKK3 and 14-3-3 is dependent on Ser526 and prevents dephosphorylation of Ser526 in HEK293 EBNA cells, Ser526 of MEKK3 is an autophosphorylation site within the T-loop that is regulated by PP2A and 14-3-3 proteins
additional information
-
two isoforms of MEKK4, monitors the integrity of the actin cytoskeleton and regulates its recovery from osmotic stress, MEKK4 and TRAF4 are involved in the process of neurulation
additional information
-
two isoforms of MEKK4, play a role in downregulating apoptosis during neurulation via the p38 MAPK pathway
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Hunter, T.
Protein kinases and phosphatases: the yin and yang of protein phosphorylation and signaling
Cell
80
225-236
1995
eukaryota
brenda
Wood, V.; Gwilliam, R.; Rajandream, M.A.; Lyne, M.; Lyne, R.; et al.
The genome sequence of Schizosaccharomyces pombe
Nature
415
871-880
2002
Schizosaccharomyces pombe (O14299), Schizosaccharomyces pombe (O74304), Schizosaccharomyces pombe (P28829), Schizosaccharomyces pombe (Q10407)
brenda
Ito, M.; Yoshioka, K.; Akechi, M.; Yamashita, S.; Takamatsu, N.; Sugiyama, K.; Hibi, M.; Nakabeppu, Y.; Shiba, T.; Yamamoto, K.I.
JSAP1, a novel jun N-terminal protein kinase (JNK)-binding protein that functions as a Scaffold factor in the JNK signaling pathway
Mol. Cell. Biol.
19
7539-7548
1999
Mus musculus (P53349), Mus musculus
brenda
Gerwins, P.; Blank, J.L.; Johnson, G.L.
Cloning of a novel mitogen-activated protein kinase kinase kinase, MEKK4, that selectively regulates the c-Jun amino terminal kinase pathway
J. Biol. Chem.
272
8288-8295
1997
Mus musculus (O08648), Mus musculus
brenda
Schweifer, N.; Valk, P.J.; Delwel, R.; Cox, R.; Francis, F.; Meier-Ewert, S.; Lehrach, H.; Barlow, D.P.
Characterization of the C3 YAC contig from proximal mouse chromosome 17 and analysis of allelic expression of genes flanking the imprinted Igf2r gene
Genomics
43
285-297
1997
Mus musculus (O08648)
brenda
Samejima, I.; Mackie, S.; Fantes, P.A.
Multiple modes of activation of the stress-responsive MAP kinase pathway in fission yeast
EMBO J.
16
6162-6170
1997
Schizosaccharomyces pombe (O14299), Schizosaccharomyces pombe
brenda
Shieh, J.C.; Wilkinson, M.G.; Buck, V.; Morgan, B.A.; Makino, K.; Millar, J.B.
The Mcs4 response regulator coordinately controls the stress-activated Wak1-Wis1-Sty1 MAP kinase pathway and fission yeast cell cycle
Genes Dev.
11
1008-1022
1997
Schizosaccharomyces pombe (O14299), Schizosaccharomyces pombe
brenda
Shiozaki, K.; Shiozaki, M.; Russell, P.
Mcs4 mitotic catastrophe suppressor regulates the fission yeast cell cycle through the Wik1-Wis1-Spc1 kinase cascade
Mol. Biol. Cell
8
409-419
1997
Schizosaccharomyces pombe (O14299), Schizosaccharomyces pombe
brenda
Samejima, I.; Mackie, S.; Warbrick, E.; Weisman, R.; Fantes, P.A.
The fission yeast mitotic regulator win1+ encodes an MAP kinase kinase kinase that phosphorylates and activates Wis1 MAP kinase kinase in response to high osmolarity
Mol. Biol. Cell
9
2325-2335
1998
Schizosaccharomyces pombe (O74304), Schizosaccharomyces pombe
brenda
Wang, X.S.; Diener, K.; Tan, T.H.; Yao, Z.
MAPKKK6, a novel mitogen-activated protein kinase kinase kinase, that associates with MAPKKK5
Biochem. Biophys. Res. Commun.
253
33-37
1998
Homo sapiens (O95382)
brenda
Cairns, B.R.; Ramer, S.W.; Kornberg, R.D.
Order of action of components in the yeast pheromone response pathway revealed with a dominant allele of the STE11 kinase and the multiple phosphorylation of the STE7 kinase
Genes Dev.
6
1305-1318
1992
Saccharomyces cerevisiae (P23561), Saccharomyces cerevisiae
brenda
Maeda, T.; Takekawa, M.; Saito, H.
Activation of yeast PBS2 MAPKK by MAPKKKs or by binding of an SH3-containing osmosensor
Science
269
554-558
1995
Saccharomyces cerevisiae (P53599), Saccharomyces cerevisiae
brenda
Rhodes, N.; Connell, L.; Errede, B.
STE11 is a protein kinase required for cell-type-specific transcription and signal transduction in yeast
Genes Dev.
4
1862-1874
1990
Saccharomyces cerevisiae (P23561), Saccharomyces cerevisiae
brenda
Styrkarsdottir, U.; Egel, R.; Nielsen, O.
Functional conservation between Schizosaccharomyces pombe ste8 and Saccharomyces cerevisiae STE11 protein kinases in yeast signal transduction
Mol. Gen. Genet.
235
122-130
1992
Schizosaccharomyces pombe (P28829), Schizosaccharomyces pombe
brenda
Wang, Y.; Xu, H.P.; Riggs, M.; Rodgers, L.; Wigler, M.
Byr2, a Schizosaccharomyces pombe gene encoding a protein kinase capable of partial suppression of the ras1 mutant phenotype
Mol. Cell. Biol.
11
3554-3563
1991
Schizosaccharomyces pombe (P28829)
brenda
Lange-Carter, C.A.; Pleiman, C.M.; Gardner, A.M.; Blumer, K.J.; Johnson, G.L.
A divergence in the MAP kinase regulatory network defined by MEK kinase and Raf
Science
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Mus musculus (P53349), Mus musculus
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Sengar, A.S.; Markley, N.A.; Marini, N.J.; Young, D.
Mkh1, a MEK kinase required for cell wall integrity and proper response to osmotic and temperature stress in Schizosaccharomyces pombe
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Schizosaccharomyces pombe (Q10407), Schizosaccharomyces pombe
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Saccharomyces cerevisiae
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Ras and mitogen-activated protein kinase kinase kinase-1 coregulate activator protein-1- and nuclear factor-kappaB-mediated gene expression in airway epithelial cells
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Homo sapiens
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Purification and kinetic characterization of recombinant human mitogen-activated protein kinase kinase kinase COT and the complexes with its cellular partner NF-kappa B1 p105
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Homo sapiens
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Mutations in protein kinase subdomain X differentially affect MEKK2 and MEKK1 activity
Biochem. Biophys. Res. Commun.
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Mus musculus
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Channavajhala, P.L.; Rao, V.R.; Spaulding, V.; Lin, L.L.; Zhang, Y.G.
hKSR-2 inhibits MEKK3-activated MAP kinase and NF-kappaB pathways in inflammation
Biochem. Biophys. Res. Commun.
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Homo sapiens (Q6VAB6), Homo sapiens
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Rattus norvegicus
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Cloning and expression analysis of a MAPKKK gene and a novel nodulin gene of Lotus japonicus
Biosci. Biotechnol. Biochem.
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Lotus japonicus (Q75PK5), Lotus japonicus
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Roles of MAPKKK ASK1 in stress-induced cell death
Cell Struct. Funct.
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Caenorhabditis elegans, Homo sapiens, Mus musculus
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Poitras, L.; Bisson, N.; Islam, N.; Moss, T.
A tissue restricted role for the Xenopus Jun N-terminal kinase kinase kinase MLK2 in cement gland and pronephric tubule differentiation
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Xenopus laevis
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Cuevas, B.D.; Abell, A.N.; Witowsky, J.A.; Yujiri, T.; Johnson, N.L.; Kesavan, K.; Ware, M.; Jones, P.L.; Weed, S.A.; DeBiasi, R.L.; Oka, Y.; Tyler, K.L.; Johnson, G.L.
MEKK1 regulates calpain-dependent proteolysis of focal adhesion proteins for rear-end detachment of migrating fibroblasts
EMBO J.
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Mus musculus
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del Pozo, O.; Pedley, K.F.; Martin, G.B.
MAPKKKalpha is a positive regulator of cell death associated with both plant immunity and disease
EMBO J.
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Solanum lycopersicum (Q6RFY3), Nicotiana benthamiana (Q6RFY4)
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Identification of MEKK2/3 serine phosphorylation site targeted by the Toll-like receptor and stress pathways
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Mus musculus
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Kicka, S.; Silar, P.
PaASK1, a mitogen-activated protein kinase kinase kinase that controls cell degeneration and cell differentiation in Podospora anserina
Genetics
166
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2004
Podospora anserina
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Takahashi, M.; Gotoh, Y.; Isagawa, T.; Nishimura, T.; Goyama, E.; Kim, H.S.; Mukai, H.; Ono, Y.
Regulation of a mitogen-activated protein kinase kinase kinase, MLTK by PKN
J. Biochem.
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2003
Homo sapiens
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Witowsky, J.A.; Johnson, G.L.
Ubiquitylation of MEKK1 inhibits its phosphorylation of MKK1 and MKK4 and activation of the ERK1/2 and JNK pathways
J. Biol. Chem.
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Mus musculus
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Calipel, A.; Lefevre, G.; Pouponnot, C.; Mouriaux, F.; Eychene, A.; Mascarelli, F.
Mutation of B-Raf in human choroidal melanoma cells mediates cell proliferation and transformation through the MEK/ERK Pathway
J. Biol. Chem.
278
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Homo sapiens
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Tu, Z.; Lee, F.S.
Subdomain VIII is a specificity-determining region in MEKK1
J. Biol. Chem.
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Mus musculus
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Machida, N.; Umikawa, M.; Takei, K.; Sakima, N.; Myagmar, B.E.; Taira, K.; Uezato, H.; Ogawa, Y.; Kariya, K.
Mitogen-activated protein kinase kinase kinase kinase 4 as a putative effector of Rap2 to activate the c-Jun N-terminal kinase
J. Biol. Chem.
279
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Medicago sativa (Q7XTK4)
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Samanta, A.K.; Huang, H.J.; Bast, R.C., Jr.; Liao, W.S.
Overexpression of MEKK3 confers resistance to apoptosis through activation of NFkappaB
J. Biol. Chem.
279
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Homo sapiens
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Xu, B.E.; Stippec, S.; Lenertz, L.; Lee, B.H.; Zhang, W.; Lee, Y.K.; Cobb, M.H.
WNK1 activates ERK5 by an MEKK2/3-dependent mechanism
J. Biol. Chem.
279
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Homo sapiens
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Robitaille, H.; Proulx, R.; Robitaille, K.; Blouin, R.; Germain, L.
The mitogen-activated protein kinase kinase kinase dual leucine zipper-bearing kinase (DLK) acts as a key regulator of keratinocyte terminal differentiation
J. Biol. Chem.
280
12732-12741
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Homo sapiens
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Cheng, J.; Yu, L.; Zhang, D.; Huang, Q.; Spencer, D.; Su, B.
Dimerization through the catalytic domain is essential for MEKK2 activation
J. Biol. Chem.
280
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Mus musculus
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Fritz, A.; Brayer, K.J.; McCormick, N.; Adams, D.G.; Wadzinski, B.E.; Vaillancourt, R.R.
Phosphorylation of serine 526 is required for MEKK3 activity and association with 14-3-3 blocks dephosphorylation
J. Biol. Chem.
281
6236-6245
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Homo sapiens, Mus musculus, synthetic construct
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Du, J.; Cai, S.; Suzuki, H.; Akhand, A.A.; Ma, X.; Takagi, Y.; Miyata, T.; Nakashima, I.; Nagase, F.
Involvement of MEKK1/ERK/p21Waf1/Cip1 signal transduction pathway in inhibition of IGF-I-mediated cell growth response by methylglyoxal
J. Cell. Biochem.
88
1235-1246
2003
Homo sapiens, Mus musculus
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Kwan, J.J.; Warner, N.; Maini, J.; Chan Tung, K.W.; Zakaria, H.; Pawson, T.; Donaldson, L.W.
Saccharomyces cerevisiae Ste50 binds the MAPKKK Ste11 through a head-to-tail SAM domain interaction
J. Mol. Biol.
356
142-154
2006
Saccharomyces cerevisiae
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Takekawa, M.; Tatebayashi, K.; Saito, H.
Conserved docking site is essential for activation of mammalian MAP kinase kinases by specific MAP kinase kinase kinases
Mol. Cell
18
295-306
2005
Homo sapiens
brenda
Yue, J.; Xiong, W.; Ferrell, J.E.
B-Raf and C-Raf are required for Ras-stimulated p42 MAP kinase activation in Xenopus egg extracts
Oncogene
1
1-9
2006
Xenopus laevis
brenda
Bergmann, D.C.; Lukowitz, W.; Somerville, C.R.
Stomatal development and pattern controlled by a MAPKK kinase
Science
304
1494-1497
2004
Arabidopsis thaliana
brenda
Hu, Q.; Shen, W.; Huang, H.; Liu, J.; Zhang, J.; Huang, X.; Wu, J.; Shi, Y.
Insight into the binding properties of MEKK3 PB1 to MEK5 PB1 from its solution structure
Biochemistry
46
13478-13489
2007
Homo sapiens
brenda
Stevens, M.V.; Parker, P.; Vaillancourt, R.R.; Camenisch, T.D.
MEKK4 regulates developmental EMT in the embryonic heart
Dev. Dyn.
235
2761-2770
2006
Mus musculus
brenda
Oetjen, E.; Blume, R.; Cierny, I.; Schlag, C.; Kutschenko, A.; Kraetzner, R.; Stein, R.; Knepel, W.
Inhibition of MafA transcriptional activity and human insulin gene transcription by interleukin-1beta and mitogen-activated protein kinase kinase kinase in pancreatic islet beta cells
Diabetologia
50
1678-1687
2007
synthetic construct
brenda
Faour, W.H.; He, Q.; Mancini, A.; Jovanovic, D.; Antoniou, J.; Di Battista, J.A.
Prostaglandin E2 stimulates p53 transactivational activity through specific serine 15 phosphorylation in human synovial fibroblasts. Role in suppression of c/EBP/NF-kappaB-mediated MEKK1-induced MMP-1 expression
J. Biol. Chem.
281
19849-19860
2006
Homo sapiens
brenda
Ichimura, K.; Casais, C.; Peck, S.C.; Shinozaki, K.; Shirasu, K.
MEKK1 is required for MPK4 activation and regulates tissue-specific and temperature-dependent cell death in Arabidopsis
J. Biol. Chem.
281
36969-36976
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Arabidopsis thaliana (Q39008)
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Nakagami, H.; Soukupova, H.; Schikora, A.; Zarsky, V.; Hirt, H.
A Mitogen-activated protein kinase kinase kinase mediates reactive oxygen species homeostasis in Arabidopsis
J. Biol. Chem.
281
38697-38704
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Arabidopsis thaliana
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Takeda, K.; Shimozono, R.; Noguchi, T.; Umeda, T.; Morimoto, Y.; Naguro, I.; Tobiume, K.; Saitoh, M.; Matsuzawa, A.; Ichijo, H.
Apoptosis signal-regulating kinase (ASK) 2 functions as a mitogen-activated protein kinase kinase kinase in a heteromeric complex with ASK1
J. Biol. Chem.
282
7522-7531
2007
Homo sapiens (O95382), Mus musculus (Q9WTR2)
brenda
Bettinger, B.T.; Amberg, D.C.
The MEK kinases MEKK4/Ssk2p facilitate complexity in the stress signaling responses of diverse systems
J. Cell. Biochem.
101
34-43
2007
Saccharomyces cerevisiae, Drosophila melanogaster, Homo sapiens, Mus musculus
brenda
Gray-Mitsumune, M.; OBrien, M.; Bertrand, C.; Tebbji, F.; Nantel, A.; Matton, D.P.
Loss of ovule identity induced by overexpression of the fertilization-related kinase 2 (ScFRK2), a MAPKKK from Solanum chacoense
J. Exp. Bot.
57
4171-4187
2006
Solanum chacoense (Q6EE08), Solanum chacoense (Q6EE09), Solanum chacoense
brenda
Chen, Z.; Cobb, M.H.
Activation of MEKK1 by Rho GTPases
Methods Enzymol.
406
468-478
2006
Homo sapiens, Mus musculus, synthetic construct
brenda
Deng, M.; Chen, W.L.; Takatori, A.; Peng, Z.; Zhang, L.; Mongan, M.; Parthasarathy, R.; Sartor, M.; Miller, M.; Yang, J.; Su, B.; Kao, W.W.; Xia, Y.
A role for the mitogen-activated protein kinase kinase kinase 1 in epithelial wound healing
Mol. Biol. Cell
17
3446-3455
2006
Mus musculus
brenda
Oida, Y.; Gopalan, B.; Miyahara, R.; Branch, C.D.; Chiao, P.; Chada, S.; Ramesh, R.
Inhibition of nuclear factor-kappaB augments antitumor activity of adenovirus-mediated melanoma differentiation-associated gene-7 against lung cancer cells via mitogen-activated protein kinase kinase kinase 1 activation
Mol. Cancer Ther.
6
1440-1449
2007
Homo sapiens
brenda
Shi, C.S.; Huang, N.N.; Harrison, K.; Han, S.B.; Kehrl, J.H.
The mitogen-activated protein kinase kinase kinase kinase GCKR positively regulates canonical and noncanonical Wnt signaling in B lymphocytes
Mol. Cell. Biol.
26
6511-6521
2006
Homo sapiens, Mus musculus, Mus musculus C57BL/6
brenda
Jonas, B.A.; Varlakhanova, N.; Hayakawa, F.; Goodson, M.; Privalsky, M.L.
Response of SMRT (silencing mediator of retinoic acid and thyroid hormone receptor) and N-CoR (nuclear receptor corepressor) corepressors to mitogen-activated protein kinase kinase kinase cascades is determined by alternative mRNA splicing
Mol. Endocrinol.
21
1924-1939
2007
synthetic construct
brenda
Cuevas, B.D.; Abell, A.N.; Johnson, G.L.
Role of mitogen-activated protein kinase kinase kinases in signal integration
Oncogene
26
3159-3171
2007
Homo sapiens, Mus musculus, Rattus norvegicus, Xenopus sp.
brenda
Miao, Y.; Laun, T.M.; Smykowski, A.; Zentgraf, U.
Arabidopsis MEKK1 can take a short cut: it can directly interact with senescence-related WRKY53 transcription factor on the protein level and can bind to its promoter
Plant Mol. Biol.
65
63-76
2007
Arabidopsis thaliana
brenda
Suarez-Rodriguez, M.C.; Adams-Phillips, L.; Liu, Y.; Wang, H.; Su, S.H.; Jester, P.J.; Zhang, S.; Bent, A.F.; Krysan, P.J.
MEKK1 is required for flg22-induced MPK4 activation in Arabidopsis plants
Plant Physiol.
143
661-669
2007
Arabidopsis thaliana
brenda
Symons, A.; Beinke, S.; Ley, S.C.
MAP kinase kinase kinases and innate immunity
Trends Immunol.
27
40-48
2006
Drosophila melanogaster, Homo sapiens, Mus musculus
brenda
Winkel, A.; Stricker, S.; Tylzanowski, P.; Seiffart, V.; Mundlos, S.; Gross, G.; Hoffmann, A.
Wnt-ligand-dependent interaction of TAK1 (TGF-beta-activated kinase-1) with the receptor tyrosine kinase Ror2 modulates canonical Wnt-signalling
Cell. Signal.
20
2134-2144
2008
Mus musculus (Q62073)
brenda
Di, Y.; Li, S.; Wang, L.; Zhang, Y.; Dorf, M.E.
Homeostatic interactions between MEKK3 and TAK1 involved in NF-kappaB signaling
Cell. Signal.
20
705-713
2008
Mus musculus
brenda
Craig, E.A.; Stevens, M.V.; Vaillancourt, R.R.; Camenisch, T.D.
MAP3Ks as central regulators of cell fate during development
Dev. Dyn.
237
3102-3114
2008
Mus musculus
brenda
Park, G.; Pan, S.; Borkovich, K.A.
A MAP kinase cascade required for regulation of development and secondary metabolism in Neurospora crassa
Eukaryot. Cell
7
2113-22
2008
Neurospora crassa
brenda
Horie, T.; Tatebayashi, K.; Yamada, R.; Saito, H.
Phosphorylated Ssk1 prevents unphosphorylated Ssk1 from activating the Ssk2 mitogen-activated protein kinase kinase kinase in the yeast high-osmolarity glycerol osmoregulatory pathway
Mol. Cell. Biol.
28
5172-5183
2008
Saccharomyces cerevisiae
brenda
Jeon, J.; Goh, J.; Yoo, S.; Chi, M.H.; Choi, J.; Rho, H.S.; Park, J.; Han, S.S.; Kim, B.R.; Park, S.Y.; Kim, S.; Lee, Y.H.
A putative MAP kinase kinase kinase, MCK1, is required for cell wall integrity and pathogenicity of the rice blast fungus, Magnaporthe oryzae
Mol. Plant Microbe Interact.
21
525-534
2008
Pyricularia oryzae
brenda
Mongan, M.; Tan, Z.; Chen, L.; Peng, Z.; Dietsch, M.; Su, B.; Leikauf, G.; Xia, Y.
Mitogen-activated protein kinase kinase kinase 1 protects against nickel-induced acute lung injury
Toxicol. Sci.
104
405-411
2008
Mus musculus
brenda
Sun, W.; Wang, H.; Zhao, X.; Yu, Y.; Fan, Y.; Wang, H.; Wang, X.; Lu, X.; Zhang, G.; Fu, S.; Yang, J.
Protein phosphatase 2A acts as a mitogen-activated protein kinase kinase kinase 3 (MEKK3) phosphatase to inhibit lysophosphatidic acid-induced IkappaB kinase beta /nuclear factor-kappaB activation
J. Biol. Chem.
285
21341-21348
2010
Homo sapiens (Q99759)
brenda
Yang, Q.; Yan, L.; Gu, Q.; Ma, Z.
The mitogen-activated protein kinase kinase kinase BcOs4 is required for vegetative differentiation and pathogenicity in Botrytis cinerea
Appl. Microbiol. Biotechnol.
96
481-492
2012
Botrytis cinerea (I7FWY1), Botrytis cinerea, Botrytis cinerea 38B1 (I7FWY1)
brenda
Li, L.; Ye, C.; Zhao, R.; Li, X.; Liu, W.Z.; Wu, F.; Yan, J.; Jiang, Y.Q.; Yang, B.
Mitogen-activated protein kinase kinase kinase (MAPKKK) 4 from rapeseed (Brassica napus L.) is a novel member inducing ROS accumulation and cell death
Biochem. Biophys. Res. Commun.
467
792-797
2015
Brassica napus (A0A0U1XFB1), Brassica napus (A0A0U1XFE3)
brenda
Feng, K.; Liu, F.; Zou, J.; Xing, G.; Deng, P.; Song, W.; Tong, W.; Nie, X.
Genome-wide identification, evolution, and co-expression network analysis of mitogen-activated protein kinase kinase kinases in Brachypodium distachyon
Front. Plant Sci.
7
1400
2016
Brachypodium distachyon
brenda
Zhou, X.; Ma, Y.; Sugiura, R.; Kobayashi, D.; Suzuki, M.; Deng, L.; Kuno, T.
MAP kinase kinase kinase (MAPKKK)-dependent and -independent activation of Sty1 stress MAPK in fission yeast
J. Biol. Chem.
285
32818-32823
2010
Schizosaccharomyces pombe (O14299), Schizosaccharomyces pombe (O74304), Schizosaccharomyces pombe, Schizosaccharomyces pombe 972 (O14299), Schizosaccharomyces pombe 972 (O74304)
brenda
Schichl, Y.M.; Resch, U.; Lemberger, C.E.; Stichlberger, D.; de Martin, R.
Novel phosphorylation-dependent ubiquitination of tristetraprolin by mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase 1 (MEKK1) and tumor necrosis factor receptor-associated factor 2 (TRAF2)
J. Biol. Chem.
286
38466-38477
2011
Homo sapiens (Q13233)
brenda
Sun, Y.; Wang, C.; Yang, B.; Wu, F.; Hao, X.; Liang, W.; Niu, F.; Yan, J.; Zhang, H.; Wang, B.; Deyholos, M.K.; Jiang, Y.Q.
Identification and functional analysis of mitogen-activated protein kinase kinase kinase (MAPKKK) genes in canola (Brassica napus L.)
J. Exp. Bot.
65
2171-2188
2014
Brassica napus, Brassica napus (V9LY75), Brassica napus (V9LYK6)
brenda
Lafleur, E.; Kapfer, C.; Joly, V.; Liu, Y.; Tebbji, F.; Daigle, C.; Gray-Mitsumune, M.; Cappadocia, M.; Nantel, A.; Matton, D.P.
The FRK1 mitogen-activated protein kinase kinase kinase (MAPKKK) from Solanum chacoense is involved in embryo sac and pollen development
J. Exp. Bot.
66
1833-1843
2015
Solanum chacoense (T2B355), Solanum chacoense
brenda
Tan, L.; Nomanbhoy, T.; Gurbani, D.; Patricelli, M.; Hunter, J.; Geng, J.; Herhaus, L.; Zhang, J.; Pauls, E.; Ham, Y.; Choi, H.G.; Xie, T.; Deng, X.; Buhrlage, S.J.; Sim, T.; Cohen, P.; Sapkota, G.; Westover, K.D.; Gray, N.S.
Discovery of type II inhibitors of TGFbeta-activated kinase 1 (TAK1) and mitogen-activated protein kinase kinase kinase kinase 2 (MAP4K2)
J. Med. Chem.
58
183-196
2015
Homo sapiens
brenda
Itoh, A.; Horiuchi, M.; Wakayama, K.; Xu, J.; Bannerman, P.; Pleasure, D.; Itoh, T.
ZPK/DLK, a mitogen-activated protein kinase kinase kinase, is a critical mediator of programmed cell death of motoneurons
J. Neurosci.
31
7223-7228
2011
Mus musculus (Q60700)
brenda
Lee, S.J.; Lee, M.H.; Kim, J.I.; Kim, S.Y.
Arabidopsis putative MAP kinase kinase kinases Raf10 and Raf11 are positive regulators of seed dormancy and ABA response
Plant Cell Physiol.
56
84-97
2015
Arabidopsis thaliana (F4HVH9), Arabidopsis thaliana (F4K645), Arabidopsis thaliana Col-0 (F4HVH9), Arabidopsis thaliana Col-0 (F4K645)
brenda
Ning, J.; Zhang, B.; Wang, N.; Zhou, Y.; Xiong, L.
Increased leaf angle1, a Raf-like MAPKKK that interacts with a nuclear protein family, regulates mechanical tissue formation in the Lamina joint of rice
Plant Cell
23
4334-4347
2011
Oryza sativa
brenda
Kong, Q.; Qu, N.; Gao, M.; Zhang, Z.; Ding, X.; Yang, F.; Li, Y.; Dong, O.X.; Chen, S.; Li, X.; Zhang, Y.
The MEKK1-MKK1/MKK2-MPK4 kinase cascade negatively regulates immunity mediated by a mitogen-activated protein kinase kinase kinase in Arabidopsis
Plant Cell
24
2225-2236
2012
Arabidopsis thaliana (O81472), Arabidopsis thaliana (Q39008), Arabidopsis thaliana, Arabidopsis thaliana Col-0 (O81472), Arabidopsis thaliana Col-0 (Q39008)
brenda
Kong, X.; Lv, W.; Zhang, D.; Jiang, S.; Zhang, S.; Li, D.
Genome-wide identification and analysis of expression profiles of maize mitogen-activated protein kinase kinase kinase
PLoS ONE
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e57714
2013
Zea mays
brenda
Geh, E.; Meng, Q.; Mongan, M.; Wang, J.; Takatori, A.; Zheng, Y.; Puga, A.; Lang, R.A.; Xia, Y.
Mitogen-activated protein kinase kinase kinase 1 (MAP3K1) integrates developmental signals for eyelid closure
Proc. Natl. Acad. Sci. USA
108
17349-17354
2011
Mus musculus (P53349)
brenda
Wang, X.; Hou, Y.; Deng, K.; Zhang, Y.; Wang, D.C.; Ding, J.
Structural insights into the molecular recognition between cerebral cavernous malformation 2 and mitogen-activated protein kinase kinase kinase 3
Structure
23
1087-1096
2015
Homo sapiens (Q99759)
brenda
Kim, S.; Ezhilarasan, R.; Phillips, E.; Gallego-Perez, D.; Sparks, A.; Taylor, D.; Ladner, K.; Furuta, T.; Sabit, H.; Chhipa, R.; Cho, J.; Mohyeldin, A.; Beck, S.; Kurozumi, K.; Kuroiwa, T.; Iwata, R.; Asai, A.; Kim, J.; Sulman, E.; Cheng, S.; Lee, L.
Serine/threonine kinase MLK4 determines mesenchymal identity in glioma stem cells in an NF-kappaB-dependent manner
Cancer Cell
29
201-213
2016
Homo sapiens (Q5TCX8)
brenda
Aramini, J.; Vorobiev, S.; Tuberty, L.; Janjua, H.; Campbell, E.; Seetharaman, J.; Su, M.; Huang, Y.; Acton, T.; Xiao, R.; Tong, L.; Montelione, G.
The RAS-binding domain of human BRAF protein serine/threonine kinase exhibits allosteric conformational changes upon binding HRAS
Structure
23
1382-1393
2015
Homo sapiens
brenda
Wang, M.; Yue, H.; Feng, K.; Deng, P.; Song, W.; Nie, X.
Genome-wide identification, phylogeny and expressional profiles of mitogen activated protein kinase kinase kinase (MAPKKK) gene family in bread wheat (Triticum aestivum L.)
BMC Genomics
17
668
2016
Triticum aestivum
brenda
Liu, Y.; Zhu, Y.; Xu, X.; Sun, F.; Yang, J.; Cao, L.; Luo, X.
OstMAPKKK5, a truncated mitogen-activated protein kinase kinase kinase 5, positively regulates plant height and yield in rice
Crop J.
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707-714
2019
Oryza sativa Indica Group
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brenda
Mithoe, S.; Ludwig, C.; Pel, M.; Cucinotta, M.; Casartelli, A.; Mbengue, M.; Sklenar, J.; Derbyshire, P.; Robatzek, S.; Pieterse, C.; Aebersold, R.; Menke, F.
Attenuation of pattern recognition receptor signaling is mediated by a MAP kinase kinase kinase
EMBO Rep.
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441-454
2016
Arabidopsis thaliana
brenda
Liu, G.; Chen, M.; Yu, C.; Wang, W.; Yang, L.; Li, Z.; Wang, W.; Chen, J.
Molecular cloning, characterization and functional analysis of a putative mitogen-activated protein kinase kinase kinase 4 (MEKK4) from blood clam Tegillarca granosa
Fish Shellfish Immunol.
66
372-381
2017
Tegillarca granosa (A0A1X9RHQ4)
brenda
Benhamman, R.; Bai, F.; Drory, S.; Loubert-Hudon, A.; Ellis, B.; Matton, D.
The Arabidopsis mitogen-activated protein kinase kinase kinase 20 (MKKK20) acts upstream of MKK3 and MPK18 in two separate signaling pathways involved in root microtubule functions
Front. Plant Sci.
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1352
2017
Arabidopsis thaliana, Arabidopsis thaliana (Q9SND6)
brenda
Antonucci, L.; Di Magno, L.; DAmico, D.; Manni, S.; Serrao, S.; Pastena, F.; Bordone, R.; Yurtsever, Z.; Caimano, M.; Petroni, M.; Giorgi, A.; Schinin, M.; Yates, J.I.; Marcotullio, L.; Smaele, E.; Checquolo, S.; Capalbo, C.; Agostinelli, E.; Maroder, M
Mitogen-activated kinase kinase kinase 1 inhibits hedgehog signaling and medulloblastoma growth through GLI1 phosphorylation
Int. J. Oncol.
54
505-514
2019
Homo sapiens
brenda
Guo, C.; Yu, M.; Dai, J.; Pan, S.; Lu, Z.; Qiu, X.; Zhuan, Z.
Roles of mitogen-activating protein kinase kinase kinase kinase-3 (MAP4K3) in preterm skeletal muscle satellite cell myogenesis and mammalian target of rapamycin complex 1 (mTORC1) activation regulation
Med. Sci. Monit.
23
3562-3570
2017
Rattus norvegicus (Q924I2)
brenda
Zhang, F.; Huang, L.; Deng, J.; Tan, C.; Geng, L.; Liao, Y.; Yuan, J.; Wang, S.
A cell wall integrity-related MAP kinase kinase kinase AflBck1 is required for growth and virulence in fungus Aspergillus flavus
Mol. Plant Microbe Interact.
33
680-692
2020
Aspergillus flavus
brenda
Wang, B.; Liu, G.; Zhang, J.; Li, Y.; Yang, H.; Ren, D.
The RAF-like mitogen-activated protein kinase kinase kinases RAF22 and RAF28 are required for the regulation of embryogenesis in Arabidopsis
Plant J.
96
734-747
2018
Arabidopsis thaliana
brenda
Bai, F.; Matton, D.
The Arabidopsis mitogen-activated protein kinase kinase kinase 20(MKKK20) C-terminal domain interacts with MKK3 and harbors a typical DEF mammalian MAP kinase docking site
Plant Signal. Behav.
13
e1503498
2018
Arabidopsis thaliana (Q9SND6), Arabidopsis thaliana
brenda
Mazin, B.; Joly, V.; Matton, D.
The ScFRK2 mitogen-activated protein kinase kinase kinase (MAP3K) is involved in early embryo sac development in Solanum chacoense
Plant Signal. Behav.
14
e1620059
2019
Solanum chacoense
brenda
Zhang, D.; Liu, Y.; Cui, Y.; Cui, S.
Mitogen-activated protein kinase kinase kinase 8 (MAP3K8) mediates the LH-induced stimulation of progesterone synthesis in the porcine corpus luteum
Reprod. Fertil. Dev.
31
1444-1456
2019
Sus scrofa
brenda
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Release 2023.1 (January 2023)
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