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Literature summary for 2.7.11.25 extracted from

  • 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) (2011), J. Biol. Chem., 286, 38466-38477.
    View publication on PubMedView publication on EuropePMC
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Protein Variants

Protein Variants Comment Organism
additional information lentiviral, shRNA-mediated MEKK1 knockdown in HUVEC. Generation of a dominant negative MEKK1 mutant Homo sapiens

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + tristetraprolin Homo sapiens
-
 ADP + phosphorylated tristetraprolin
-
 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens Q13233
-
-

Posttranslational Modification

Posttranslational Modification Comment Organism
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 Homo sapiens

Source Tissue

Source Tissue Comment Organism Textmining
HEK-293 cell
-
 Homo sapiens
-
HeLa cell
-
 Homo sapiens
-
umbilical vein endothelial cell
-
 Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + tristetraprolin
-
 Homo sapiens ADP + phosphorylated tristetraprolin
-
 ?
ATP + tristetraprolin i.e. TTP, physical interaction of MEKK1 with TTP Homo sapiens ADP + phosphorylated tristetraprolin
-
 ?

Subunits

Subunits Comment Organism
More MEKK1 has a kinase domain at its C-terminus, and a PHD domain at its N-terminus responsible for its E3 ligase activity Homo sapiens

Synonyms

Synonyms Comment Organism
MAP 3-kinase
-
 Homo sapiens
MEKK1
-
 Homo sapiens
mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase 1
-
 Homo sapiens
TTP kinase
-
 Homo sapiens

Cofactor

Cofactor Comment Organism Structure
ATP
-
 Homo sapiens

General Information

General Information Comment Organism
malfunction mutation of either MEKK1 or TRAF2 impairs TTP ubiquitination, whereas mutation of both completely abolishes TTP ubiquitination Homo sapiens
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 Homo sapiens
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 Homo sapiens
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 Homo sapiens