Information on EC 2.7.11.24 - mitogen-activated protein kinase and Organism(s) Caenorhabditis elegans

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The enzyme appears in selected viruses and cellular organisms

EC NUMBER
COMMENTARY hide
2.7.11.24
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RECOMMENDED NAME
GeneOntology No.
mitogen-activated protein kinase
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phospho group transfer
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SYSTEMATIC NAME
IUBMB Comments
ATP:protein phosphotransferase (MAPKK-activated)
Phosphorylation of specific tyrosine and threonine residues in the activation loop of this enzyme by EC 2.7.12.2, mitogen-activated protein kinase kinase (MAPKK) is necessary for enzyme activation. Once activated, the enzyme phosphorylates target substrates on serine or threonine residues followed by a proline [6]. A distinguishing feature of all MAPKs is the conserved sequence Thr-Xaa-Tyr (TXY). 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.
CAS REGISTRY NUMBER
COMMENTARY hide
142243-02-5
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
C493C.10 is an orthologue of mammalian JNK; jnk-1 is an orthologue of mammalian JNK; kgb-1 is an orthologue of mammalian JNK; kgb-2 is an orthologue of mammalian JNK. The JNK homologue KGB-2 shows 84% identity with KGB-1; pmk-1 is an orthologue of mammalian p38. The three pmk genes pmk1, pmk-2, and pmk-3, are encoded by a single polycistronic transcript (operon), precluding the generation of double mutants by traditional genetic crosses; pmk-2 is an orthologue of mammalian p38. The three pmk genes pmk1, pmk-2, and pmk-3, are encoded by a single polycistronic transcript (operon), precluding the generation of double mutants by traditional genetic crosses; pmk-3 is an orthologue of mammalian p38. The three pmk genes pmk1, pmk-2, and pmk-3, are encoded by a single polycistronic transcript (operon), precluding the generation of double mutants by traditional genetic crosses
malfunction
a kgb-1 null mutant, obtained by targeted deletion, shows extra germ cells, increased number of P granules, and temperature-sensitive sterility. RNAi-mediated knockdown of glh-1 in kgb-1 mutants partially rescues the P granule number and temperature-sensitive sterility. Null mutations in vhp-1 cause larval lethality, which can be suppressed by null mutations in mlk-1, mek-1, kgb-1, dlk-1, or pmk-3; null mutations in vhp-1 cause larval lethality, which can be suppressed by null mutations in mlk-1, mek-1, kgb-1, dlk-1, or pmk-3. DLK-1/PMK-3 are identified to affect cilia length, via regulation of RAB-5 endosomes; removing the 3'-UTR of pmk-2 causes its expression in the intestine, which is sufficient to rescue the Esp phenotype of pmk-1 mutants. The Esp mutant phenotype worms show enhanced susceptibility to Pseudomonas aeruginosa that causes an intestinal infection and eventual death of the worm
metabolism
distinct p38 and JNK MAPK cascades regulate a diverse class of normal biological processes during development and nervous system function; the core MAPK signaling cassette consists of a MAPKKK/MAPKK/MAPK cascade, stress-activated MAPK components involved in non-stress-associated processes, overview; the core MAPK signaling cassette consists of a MAPKKK/MAPKK/MAPK cascade, stress-activated MAPK components involved in non-stress-associated processes, overview. Distinct p38 and JNK MAPK cascades regulate a diverse class of normal biological processes during development and nervous system function; the core MAPK signaling cassette consists of a MAPKKK/MAPKK/MAPK cascade, stress-activated MAPK components involved in non-stress-associated processes, overview. Distinct p38 and JNK MAPK cascades regulate a diverse class of normal biological processes during development and nervous system function; the core MAPK signaling cassette consists of a MAPKKK/MAPKK/MAPK cascade, stress-activated MAPK components involved in non-stress-associated processes, overview. Distinct p38 and JNK MAPK cascades regulate a diverse class of normal biological processes during development and nervous system function; the core MAPK signaling cassette consists of a MAPKKK/MAPKK/MAPK cascade, stress-activated MAPK components involved in non-stress-associated processes, overview. Distinct p38 and JNK MAPK cascades regulate a diverse class of normal biological processes during development and nervous system function. Functional redundancy of pmk-1 and pmk-2; the core MAPK signaling cassette consists of a MAPKKK/MAPKK/MAPK cascade, stress-activated MAPK components involved in non-stress-associated processes, overview. Distinct p38 and JNK MAPK cascades regulate a diverse class of normal biological processes during development and nervous system function. Functional redundancy of pmk-1 and pmk-2; the core MAPK signaling cassette consists of a MAPKKK/MAPKK/MAPK cascade, stress-activated MAPK components involved in non-stress-associated processes, overview. Distinct p38 and JNK MAPK cascades regulate a diverse class of normal biological processes during development and nervous system function. The three kinases DLK-1/MKK-4/PMK-3 constitute a linear pathway. MAK-2 is the homologue of MAPKAPK2 (MK2), and acts downstream of PMK-3. The conserved pathway, the DLK-1/MKK-4/PMK-3 cascade, activation is necessary to initiate axonal regrowth. The cascade is tightly regulated by protein ubiquitination during synapse development
physiological function
activation of JNK signaling occurs under conditions of heavy metal stress. Olfactory memory in Caenorhabditis elegans allows for the association of cues with positive or negative experiences. The loss of these memories proceeds through the UNC-43/TIR-1/NSY-1/SEK-1/JNK-1 cascade; PMK-3 acts during neuronal development. vhp-1 regulates MAP kinases in axon regeneration. svh-1 and svh-2 likely provide a layer of specificity in controlling the KGB-1/JNK pathway, independently of PMK-3 in axon injury response, crosstalk between the KGB-1 and PMK-3 cascades. The avoidance of high CO2 environments and pathogens is mediated by MOM-4/MKK-4/PMK-3 in the BAG neuron; roles for KGB-2 are in excess carbon dioxide (hypercapnia)-induced fertility defects and a slight negative role in axon injury response; the enzyme is involved in P granule formation in germ cell proliferation. KGB-1 can bind and phosphorylate GLH-1, which leads to degradation of phosphorylated GLH-1. KGB-1 activity negatively regulates GLH-1 and the steady state level of P granules to maintain fertility. vhp-1 regulates MAP kinases in axon regeneration. svh-1 and svh-2 likely provide a layer of specificity in controlling the KGB-1/JNK pathway, independently of PMK-3 in axon injury response, crosstalk between the KGB-1 and PMK-3 cascades. The aversive reaction to microbial exposure is mediated by a MLK-1/MEK-1(SEK-1)/KGB-1 pathway; the NSY-1/SEK-1/PMK-1 and PMK-2 cascade acts during neuronal development to regulate AWC asymmetry. The activation of this cascade is regulated in part by calcium, via calmodulin kinase II, as well as the conserved protein TIR-1. PMK-1 and PMK-2 act redundantly downstream of TIR-1/NSY-1/SEK-1 to induce TPH-1 expression in the ADF neuron following exposure to bacteria. Genes pmk-1 and pmk-2 function redundantly during olfactory neuronal development; the NSY-1/SEK-1/PMK-1 and PMK-2 cascade acts during neuronal development to regulate AWC asymmetry. The activation of this cascade is regulated in part by calcium, via calmodulin kinase II, as well as the conserved protein TIR-1. PMK-1 and PMK-2 act redundantly downstream of TIR-1/NSY-1/SEK-1 to induce TPH-1 expression in the ADF neuron following exposure to bacteria. Genes pmk-1 and pmk-2 function redundantly during olfactory neuronal development. Activation of PMK-1 following arsenite treatment is dependent on SEK-1 but independent of NSY-1, differing from the NSY-1/SEK-1/PMK-1 cascade used during infection and osmotic stress. Unique upstream components activating PMK-1 induce SKN-1 activation following toxin and bacterial exposure
evolution
C493C.10 is an orthologue of mammalian JNK; jnk-1 is an orthologue of mammalian JNK; kgb-1 is an orthologue of mammalian JNK; kgb-2 is an orthologue of mammalian JNK. The JNK homologue KGB-2 shows 84% identity with KGB-1; pmk-1 is an orthologue of mammalian p38. The three pmk genes pmk1, pmk-2, and pmk-3, are encoded by a single polycistronic transcript (operon), precluding the generation of double mutants by traditional genetic crosses; pmk-2 is an orthologue of mammalian p38. The three pmk genes pmk1, pmk-2, and pmk-3, are encoded by a single polycistronic transcript (operon), precluding the generation of double mutants by traditional genetic crosses; pmk-3 is an orthologue of mammalian p38. The three pmk genes pmk1, pmk-2, and pmk-3, are encoded by a single polycistronic transcript (operon), precluding the generation of double mutants by traditional genetic crosses
malfunction
a kgb-1 null mutant, obtained by targeted deletion, shows extra germ cells, increased number of P granules, and temperature-sensitive sterility. RNAi-mediated knockdown of glh-1 in kgb-1 mutants partially rescues the P granule number and temperature-sensitive sterility. Null mutations in vhp-1 cause larval lethality, which can be suppressed by null mutations in mlk-1, mek-1, kgb-1, dlk-1, or pmk-3; null mutations in vhp-1 cause larval lethality, which can be suppressed by null mutations in mlk-1, mek-1, kgb-1, dlk-1, or pmk-3. DLK-1/PMK-3 are identified to affect cilia length, via regulation of RAB-5 endosomes; removing the 3'-UTR of pmk-2 causes its expression in the intestine, which is sufficient to rescue the Esp phenotype of pmk-1 mutants. The Esp mutant phenotype worms show enhanced susceptibility to Pseudomonas aeruginosa that causes an intestinal infection and eventual death of the worm
metabolism
distinct p38 and JNK MAPK cascades regulate a diverse class of normal biological processes during development and nervous system function; the core MAPK signaling cassette consists of a MAPKKK/MAPKK/MAPK cascade, stress-activated MAPK components involved in non-stress-associated processes, overview; the core MAPK signaling cassette consists of a MAPKKK/MAPKK/MAPK cascade, stress-activated MAPK components involved in non-stress-associated processes, overview. Distinct p38 and JNK MAPK cascades regulate a diverse class of normal biological processes during development and nervous system function; the core MAPK signaling cassette consists of a MAPKKK/MAPKK/MAPK cascade, stress-activated MAPK components involved in non-stress-associated processes, overview. Distinct p38 and JNK MAPK cascades regulate a diverse class of normal biological processes during development and nervous system function; the core MAPK signaling cassette consists of a MAPKKK/MAPKK/MAPK cascade, stress-activated MAPK components involved in non-stress-associated processes, overview. Distinct p38 and JNK MAPK cascades regulate a diverse class of normal biological processes during development and nervous system function; the core MAPK signaling cassette consists of a MAPKKK/MAPKK/MAPK cascade, stress-activated MAPK components involved in non-stress-associated processes, overview. Distinct p38 and JNK MAPK cascades regulate a diverse class of normal biological processes during development and nervous system function. Functional redundancy of pmk-1 and pmk-2; the core MAPK signaling cassette consists of a MAPKKK/MAPKK/MAPK cascade, stress-activated MAPK components involved in non-stress-associated processes, overview. Distinct p38 and JNK MAPK cascades regulate a diverse class of normal biological processes during development and nervous system function. Functional redundancy of pmk-1 and pmk-2; the core MAPK signaling cassette consists of a MAPKKK/MAPKK/MAPK cascade, stress-activated MAPK components involved in non-stress-associated processes, overview. Distinct p38 and JNK MAPK cascades regulate a diverse class of normal biological processes during development and nervous system function. The three kinases DLK-1/MKK-4/PMK-3 constitute a linear pathway. MAK-2 is the homologue of MAPKAPK2 (MK2), and acts downstream of PMK-3. The conserved pathway, the DLK-1/MKK-4/PMK-3 cascade, activation is necessary to initiate axonal regrowth. The cascade is tightly regulated by protein ubiquitination during synapse development
physiological function
activation of JNK signaling occurs under conditions of heavy metal stress. Olfactory memory in Caenorhabditis elegans allows for the association of cues with positive or negative experiences. The loss of these memories proceeds through the UNC-43/TIR-1/NSY-1/SEK-1/JNK-1 cascade; PMK-3 acts during neuronal development. vhp-1 regulates MAP kinases in axon regeneration. svh-1 and svh-2 likely provide a layer of specificity in controlling the KGB-1/JNK pathway, independently of PMK-3 in axon injury response, crosstalk between the KGB-1 and PMK-3 cascades. The avoidance of high CO2 environments and pathogens is mediated by MOM-4/MKK-4/PMK-3 in the BAG neuron; roles for KGB-2 are in excess carbon dioxide (hypercapnia)-induced fertility defects and a slight negative role in axon injury response; the enzyme is involved in P granule formation in germ cell proliferation. KGB-1 can bind and phosphorylate GLH-1, which leads to degradation of phosphorylated GLH-1. KGB-1 activity negatively regulates GLH-1 and the steady state level of P granules to maintain fertility. vhp-1 regulates MAP kinases in axon regeneration. svh-1 and svh-2 likely provide a layer of specificity in controlling the KGB-1/JNK pathway, independently of PMK-3 in axon injury response, crosstalk between the KGB-1 and PMK-3 cascades. The aversive reaction to microbial exposure is mediated by a MLK-1/MEK-1(SEK-1)/KGB-1 pathway; the NSY-1/SEK-1/PMK-1 and PMK-2 cascade acts during neuronal development to regulate AWC asymmetry. The activation of this cascade is regulated in part by calcium, via calmodulin kinase II, as well as the conserved protein TIR-1. PMK-1 and PMK-2 act redundantly downstream of TIR-1/NSY-1/SEK-1 to induce TPH-1 expression in the ADF neuron following exposure to bacteria. Genes pmk-1 and pmk-2 function redundantly during olfactory neuronal development; the NSY-1/SEK-1/PMK-1 and PMK-2 cascade acts during neuronal development to regulate AWC asymmetry. The activation of this cascade is regulated in part by calcium, via calmodulin kinase II, as well as the conserved protein TIR-1. PMK-1 and PMK-2 act redundantly downstream of TIR-1/NSY-1/SEK-1 to induce TPH-1 expression in the ADF neuron following exposure to bacteria. Genes pmk-1 and pmk-2 function redundantly during olfactory neuronal development. Activation of PMK-1 following arsenite treatment is dependent on SEK-1 but independent of NSY-1, differing from the NSY-1/SEK-1/PMK-1 cascade used during infection and osmotic stress. Unique upstream components activating PMK-1 induce SKN-1 activation following toxin and bacterial exposure
evolution
C493C.10 is an orthologue of mammalian JNK; jnk-1 is an orthologue of mammalian JNK; kgb-1 is an orthologue of mammalian JNK; kgb-2 is an orthologue of mammalian JNK. The JNK homologue KGB-2 shows 84% identity with KGB-1; pmk-1 is an orthologue of mammalian p38. The three pmk genes pmk1, pmk-2, and pmk-3, are encoded by a single polycistronic transcript (operon), precluding the generation of double mutants by traditional genetic crosses; pmk-2 is an orthologue of mammalian p38. The three pmk genes pmk1, pmk-2, and pmk-3, are encoded by a single polycistronic transcript (operon), precluding the generation of double mutants by traditional genetic crosses; pmk-3 is an orthologue of mammalian p38. The three pmk genes pmk1, pmk-2, and pmk-3, are encoded by a single polycistronic transcript (operon), precluding the generation of double mutants by traditional genetic crosses
malfunction
a kgb-1 null mutant, obtained by targeted deletion, shows extra germ cells, increased number of P granules, and temperature-sensitive sterility. RNAi-mediated knockdown of glh-1 in kgb-1 mutants partially rescues the P granule number and temperature-sensitive sterility. Null mutations in vhp-1 cause larval lethality, which can be suppressed by null mutations in mlk-1, mek-1, kgb-1, dlk-1, or pmk-3; null mutations in vhp-1 cause larval lethality, which can be suppressed by null mutations in mlk-1, mek-1, kgb-1, dlk-1, or pmk-3. DLK-1/PMK-3 are identified to affect cilia length, via regulation of RAB-5 endosomes; removing the 3'-UTR of pmk-2 causes its expression in the intestine, which is sufficient to rescue the Esp phenotype of pmk-1 mutants. The Esp mutant phenotype worms show enhanced susceptibility to Pseudomonas aeruginosa that causes an intestinal infection and eventual death of the worm
metabolism
distinct p38 and JNK MAPK cascades regulate a diverse class of normal biological processes during development and nervous system function; the core MAPK signaling cassette consists of a MAPKKK/MAPKK/MAPK cascade, stress-activated MAPK components involved in non-stress-associated processes, overview; the core MAPK signaling cassette consists of a MAPKKK/MAPKK/MAPK cascade, stress-activated MAPK components involved in non-stress-associated processes, overview. Distinct p38 and JNK MAPK cascades regulate a diverse class of normal biological processes during development and nervous system function; the core MAPK signaling cassette consists of a MAPKKK/MAPKK/MAPK cascade, stress-activated MAPK components involved in non-stress-associated processes, overview. Distinct p38 and JNK MAPK cascades regulate a diverse class of normal biological processes during development and nervous system function; the core MAPK signaling cassette consists of a MAPKKK/MAPKK/MAPK cascade, stress-activated MAPK components involved in non-stress-associated processes, overview. Distinct p38 and JNK MAPK cascades regulate a diverse class of normal biological processes during development and nervous system function; the core MAPK signaling cassette consists of a MAPKKK/MAPKK/MAPK cascade, stress-activated MAPK components involved in non-stress-associated processes, overview. Distinct p38 and JNK MAPK cascades regulate a diverse class of normal biological processes during development and nervous system function. Functional redundancy of pmk-1 and pmk-2; the core MAPK signaling cassette consists of a MAPKKK/MAPKK/MAPK cascade, stress-activated MAPK components involved in non-stress-associated processes, overview. Distinct p38 and JNK MAPK cascades regulate a diverse class of normal biological processes during development and nervous system function. Functional redundancy of pmk-1 and pmk-2; the core MAPK signaling cassette consists of a MAPKKK/MAPKK/MAPK cascade, stress-activated MAPK components involved in non-stress-associated processes, overview. Distinct p38 and JNK MAPK cascades regulate a diverse class of normal biological processes during development and nervous system function. The three kinases DLK-1/MKK-4/PMK-3 constitute a linear pathway. MAK-2 is the homologue of MAPKAPK2 (MK2), and acts downstream of PMK-3. The conserved pathway, the DLK-1/MKK-4/PMK-3 cascade, activation is necessary to initiate axonal regrowth. The cascade is tightly regulated by protein ubiquitination during synapse development
physiological function
activation of JNK signaling occurs under conditions of heavy metal stress. Olfactory memory in Caenorhabditis elegans allows for the association of cues with positive or negative experiences. The loss of these memories proceeds through the UNC-43/TIR-1/NSY-1/SEK-1/JNK-1 cascade; PMK-3 acts during neuronal development. vhp-1 regulates MAP kinases in axon regeneration. svh-1 and svh-2 likely provide a layer of specificity in controlling the KGB-1/JNK pathway, independently of PMK-3 in axon injury response, crosstalk between the KGB-1 and PMK-3 cascades. The avoidance of high CO2 environments and pathogens is mediated by MOM-4/MKK-4/PMK-3 in the BAG neuron; roles for KGB-2 are in excess carbon dioxide (hypercapnia)-induced fertility defects and a slight negative role in axon injury response; the enzyme is involved in P granule formation in germ cell proliferation. KGB-1 can bind and phosphorylate GLH-1, which leads to degradation of phosphorylated GLH-1. KGB-1 activity negatively regulates GLH-1 and the steady state level of P granules to maintain fertility. vhp-1 regulates MAP kinases in axon regeneration. svh-1 and svh-2 likely provide a layer of specificity in controlling the KGB-1/JNK pathway, independently of PMK-3 in axon injury response, crosstalk between the KGB-1 and PMK-3 cascades. The aversive reaction to microbial exposure is mediated by a MLK-1/MEK-1(SEK-1)/KGB-1 pathway; the NSY-1/SEK-1/PMK-1 and PMK-2 cascade acts during neuronal development to regulate AWC asymmetry. The activation of this cascade is regulated in part by calcium, via calmodulin kinase II, as well as the conserved protein TIR-1. PMK-1 and PMK-2 act redundantly downstream of TIR-1/NSY-1/SEK-1 to induce TPH-1 expression in the ADF neuron following exposure to bacteria. Genes pmk-1 and pmk-2 function redundantly during olfactory neuronal development; the NSY-1/SEK-1/PMK-1 and PMK-2 cascade acts during neuronal development to regulate AWC asymmetry. The activation of this cascade is regulated in part by calcium, via calmodulin kinase II, as well as the conserved protein TIR-1. PMK-1 and PMK-2 act redundantly downstream of TIR-1/NSY-1/SEK-1 to induce TPH-1 expression in the ADF neuron following exposure to bacteria. Genes pmk-1 and pmk-2 function redundantly during olfactory neuronal development. Activation of PMK-1 following arsenite treatment is dependent on SEK-1 but independent of NSY-1, differing from the NSY-1/SEK-1/PMK-1 cascade used during infection and osmotic stress. Unique upstream components activating PMK-1 induce SKN-1 activation following toxin and bacterial exposure
evolution
C493C.10 is an orthologue of mammalian JNK; jnk-1 is an orthologue of mammalian JNK; kgb-1 is an orthologue of mammalian JNK; kgb-2 is an orthologue of mammalian JNK. The JNK homologue KGB-2 shows 84% identity with KGB-1; pmk-1 is an orthologue of mammalian p38. The three pmk genes pmk1, pmk-2, and pmk-3, are encoded by a single polycistronic transcript (operon), precluding the generation of double mutants by traditional genetic crosses; pmk-2 is an orthologue of mammalian p38. The three pmk genes pmk1, pmk-2, and pmk-3, are encoded by a single polycistronic transcript (operon), precluding the generation of double mutants by traditional genetic crosses; pmk-3 is an orthologue of mammalian p38. The three pmk genes pmk1, pmk-2, and pmk-3, are encoded by a single polycistronic transcript (operon), precluding the generation of double mutants by traditional genetic crosses
malfunction
a kgb-1 null mutant, obtained by targeted deletion, shows extra germ cells, increased number of P granules, and temperature-sensitive sterility. RNAi-mediated knockdown of glh-1 in kgb-1 mutants partially rescues the P granule number and temperature-sensitive sterility. Null mutations in vhp-1 cause larval lethality, which can be suppressed by null mutations in mlk-1, mek-1, kgb-1, dlk-1, or pmk-3; null mutations in vhp-1 cause larval lethality, which can be suppressed by null mutations in mlk-1, mek-1, kgb-1, dlk-1, or pmk-3. DLK-1/PMK-3 are identified to affect cilia length, via regulation of RAB-5 endosomes; removing the 3'-UTR of pmk-2 causes its expression in the intestine, which is sufficient to rescue the Esp phenotype of pmk-1 mutants. The Esp mutant phenotype worms show enhanced susceptibility to Pseudomonas aeruginosa that causes an intestinal infection and eventual death of the worm
metabolism
distinct p38 and JNK MAPK cascades regulate a diverse class of normal biological processes during development and nervous system function; the core MAPK signaling cassette consists of a MAPKKK/MAPKK/MAPK cascade, stress-activated MAPK components involved in non-stress-associated processes, overview; the core MAPK signaling cassette consists of a MAPKKK/MAPKK/MAPK cascade, stress-activated MAPK components involved in non-stress-associated processes, overview. Distinct p38 and JNK MAPK cascades regulate a diverse class of normal biological processes during development and nervous system function; the core MAPK signaling cassette consists of a MAPKKK/MAPKK/MAPK cascade, stress-activated MAPK components involved in non-stress-associated processes, overview. Distinct p38 and JNK MAPK cascades regulate a diverse class of normal biological processes during development and nervous system function; the core MAPK signaling cassette consists of a MAPKKK/MAPKK/MAPK cascade, stress-activated MAPK components involved in non-stress-associated processes, overview. Distinct p38 and JNK MAPK cascades regulate a diverse class of normal biological processes during development and nervous system function; the core MAPK signaling cassette consists of a MAPKKK/MAPKK/MAPK cascade, stress-activated MAPK components involved in non-stress-associated processes, overview. Distinct p38 and JNK MAPK cascades regulate a diverse class of normal biological processes during development and nervous system function. Functional redundancy of pmk-1 and pmk-2; the core MAPK signaling cassette consists of a MAPKKK/MAPKK/MAPK cascade, stress-activated MAPK components involved in non-stress-associated processes, overview. Distinct p38 and JNK MAPK cascades regulate a diverse class of normal biological processes during development and nervous system function. Functional redundancy of pmk-1 and pmk-2; the core MAPK signaling cassette consists of a MAPKKK/MAPKK/MAPK cascade, stress-activated MAPK components involved in non-stress-associated processes, overview. Distinct p38 and JNK MAPK cascades regulate a diverse class of normal biological processes during development and nervous system function. The three kinases DLK-1/MKK-4/PMK-3 constitute a linear pathway. MAK-2 is the homologue of MAPKAPK2 (MK2), and acts downstream of PMK-3. The conserved pathway, the DLK-1/MKK-4/PMK-3 cascade, activation is necessary to initiate axonal regrowth. The cascade is tightly regulated by protein ubiquitination during synapse development
physiological function
activation of JNK signaling occurs under conditions of heavy metal stress. Olfactory memory in Caenorhabditis elegans allows for the association of cues with positive or negative experiences. The loss of these memories proceeds through the UNC-43/TIR-1/NSY-1/SEK-1/JNK-1 cascade; PMK-3 acts during neuronal development. vhp-1 regulates MAP kinases in axon regeneration. svh-1 and svh-2 likely provide a layer of specificity in controlling the KGB-1/JNK pathway, independently of PMK-3 in axon injury response, crosstalk between the KGB-1 and PMK-3 cascades. The avoidance of high CO2 environments and pathogens is mediated by MOM-4/MKK-4/PMK-3 in the BAG neuron; roles for KGB-2 are in excess carbon dioxide (hypercapnia)-induced fertility defects and a slight negative role in axon injury response; the enzyme is involved in P granule formation in germ cell proliferation. KGB-1 can bind and phosphorylate GLH-1, which leads to degradation of phosphorylated GLH-1. KGB-1 activity negatively regulates GLH-1 and the steady state level of P granules to maintain fertility. vhp-1 regulates MAP kinases in axon regeneration. svh-1 and svh-2 likely provide a layer of specificity in controlling the KGB-1/JNK pathway, independently of PMK-3 in axon injury response, crosstalk between the KGB-1 and PMK-3 cascades. The aversive reaction to microbial exposure is mediated by a MLK-1/MEK-1(SEK-1)/KGB-1 pathway; the NSY-1/SEK-1/PMK-1 and PMK-2 cascade acts during neuronal development to regulate AWC asymmetry. The activation of this cascade is regulated in part by calcium, via calmodulin kinase II, as well as the conserved protein TIR-1. PMK-1 and PMK-2 act redundantly downstream of TIR-1/NSY-1/SEK-1 to induce TPH-1 expression in the ADF neuron following exposure to bacteria. Genes pmk-1 and pmk-2 function redundantly during olfactory neuronal development; the NSY-1/SEK-1/PMK-1 and PMK-2 cascade acts during neuronal development to regulate AWC asymmetry. The activation of this cascade is regulated in part by calcium, via calmodulin kinase II, as well as the conserved protein TIR-1. PMK-1 and PMK-2 act redundantly downstream of TIR-1/NSY-1/SEK-1 to induce TPH-1 expression in the ADF neuron following exposure to bacteria. Genes pmk-1 and pmk-2 function redundantly during olfactory neuronal development. Activation of PMK-1 following arsenite treatment is dependent on SEK-1 but independent of NSY-1, differing from the NSY-1/SEK-1/PMK-1 cascade used during infection and osmotic stress. Unique upstream components activating PMK-1 induce SKN-1 activation following toxin and bacterial exposure
evolution
C493C.10 is an orthologue of mammalian JNK; jnk-1 is an orthologue of mammalian JNK; kgb-1 is an orthologue of mammalian JNK; kgb-2 is an orthologue of mammalian JNK. The JNK homologue KGB-2 shows 84% identity with KGB-1; pmk-1 is an orthologue of mammalian p38. The three pmk genes pmk1, pmk-2, and pmk-3, are encoded by a single polycistronic transcript (operon), precluding the generation of double mutants by traditional genetic crosses; pmk-2 is an orthologue of mammalian p38. The three pmk genes pmk1, pmk-2, and pmk-3, are encoded by a single polycistronic transcript (operon), precluding the generation of double mutants by traditional genetic crosses; pmk-3 is an orthologue of mammalian p38. The three pmk genes pmk1, pmk-2, and pmk-3, are encoded by a single polycistronic transcript (operon), precluding the generation of double mutants by traditional genetic crosses
malfunction
a kgb-1 null mutant, obtained by targeted deletion, shows extra germ cells, increased number of P granules, and temperature-sensitive sterility. RNAi-mediated knockdown of glh-1 in kgb-1 mutants partially rescues the P granule number and temperature-sensitive sterility. Null mutations in vhp-1 cause larval lethality, which can be suppressed by null mutations in mlk-1, mek-1, kgb-1, dlk-1, or pmk-3; null mutations in vhp-1 cause larval lethality, which can be suppressed by null mutations in mlk-1, mek-1, kgb-1, dlk-1, or pmk-3. DLK-1/PMK-3 are identified to affect cilia length, via regulation of RAB-5 endosomes; removing the 3'-UTR of pmk-2 causes its expression in the intestine, which is sufficient to rescue the Esp phenotype of pmk-1 mutants. The Esp mutant phenotype worms show enhanced susceptibility to Pseudomonas aeruginosa that causes an intestinal infection and eventual death of the worm
metabolism
distinct p38 and JNK MAPK cascades regulate a diverse class of normal biological processes during development and nervous system function; the core MAPK signaling cassette consists of a MAPKKK/MAPKK/MAPK cascade, stress-activated MAPK components involved in non-stress-associated processes, overview; the core MAPK signaling cassette consists of a MAPKKK/MAPKK/MAPK cascade, stress-activated MAPK components involved in non-stress-associated processes, overview. Distinct p38 and JNK MAPK cascades regulate a diverse class of normal biological processes during development and nervous system function; the core MAPK signaling cassette consists of a MAPKKK/MAPKK/MAPK cascade, stress-activated MAPK components involved in non-stress-associated processes, overview. Distinct p38 and JNK MAPK cascades regulate a diverse class of normal biological processes during development and nervous system function; the core MAPK signaling cassette consists of a MAPKKK/MAPKK/MAPK cascade, stress-activated MAPK components involved in non-stress-associated processes, overview. Distinct p38 and JNK MAPK cascades regulate a diverse class of normal biological processes during development and nervous system function; the core MAPK signaling cassette consists of a MAPKKK/MAPKK/MAPK cascade, stress-activated MAPK components involved in non-stress-associated processes, overview. Distinct p38 and JNK MAPK cascades regulate a diverse class of normal biological processes during development and nervous system function. Functional redundancy of pmk-1 and pmk-2; the core MAPK signaling cassette consists of a MAPKKK/MAPKK/MAPK cascade, stress-activated MAPK components involved in non-stress-associated processes, overview. Distinct p38 and JNK MAPK cascades regulate a diverse class of normal biological processes during development and nervous system function. Functional redundancy of pmk-1 and pmk-2; the core MAPK signaling cassette consists of a MAPKKK/MAPKK/MAPK cascade, stress-activated MAPK components involved in non-stress-associated processes, overview. Distinct p38 and JNK MAPK cascades regulate a diverse class of normal biological processes during development and nervous system function. The three kinases DLK-1/MKK-4/PMK-3 constitute a linear pathway. MAK-2 is the homologue of MAPKAPK2 (MK2), and acts downstream of PMK-3. The conserved pathway, the DLK-1/MKK-4/PMK-3 cascade, activation is necessary to initiate axonal regrowth. The cascade is tightly regulated by protein ubiquitination during synapse development
physiological function
activation of JNK signaling occurs under conditions of heavy metal stress. Olfactory memory in Caenorhabditis elegans allows for the association of cues with positive or negative experiences. The loss of these memories proceeds through the UNC-43/TIR-1/NSY-1/SEK-1/JNK-1 cascade; PMK-3 acts during neuronal development. vhp-1 regulates MAP kinases in axon regeneration. svh-1 and svh-2 likely provide a layer of specificity in controlling the KGB-1/JNK pathway, independently of PMK-3 in axon injury response, crosstalk between the KGB-1 and PMK-3 cascades. The avoidance of high CO2 environments and pathogens is mediated by MOM-4/MKK-4/PMK-3 in the BAG neuron; roles for KGB-2 are in excess carbon dioxide (hypercapnia)-induced fertility defects and a slight negative role in axon injury response; the enzyme is involved in P granule formation in germ cell proliferation. KGB-1 can bind and phosphorylate GLH-1, which leads to degradation of phosphorylated GLH-1. KGB-1 activity negatively regulates GLH-1 and the steady state level of P granules to maintain fertility. vhp-1 regulates MAP kinases in axon regeneration. svh-1 and svh-2 likely provide a layer of specificity in controlling the KGB-1/JNK pathway, independently of PMK-3 in axon injury response, crosstalk between the KGB-1 and PMK-3 cascades. The aversive reaction to microbial exposure is mediated by a MLK-1/MEK-1(SEK-1)/KGB-1 pathway; the NSY-1/SEK-1/PMK-1 and PMK-2 cascade acts during neuronal development to regulate AWC asymmetry. The activation of this cascade is regulated in part by calcium, via calmodulin kinase II, as well as the conserved protein TIR-1. PMK-1 and PMK-2 act redundantly downstream of TIR-1/NSY-1/SEK-1 to induce TPH-1 expression in the ADF neuron following exposure to bacteria. Genes pmk-1 and pmk-2 function redundantly during olfactory neuronal development; the NSY-1/SEK-1/PMK-1 and PMK-2 cascade acts during neuronal development to regulate AWC asymmetry. The activation of this cascade is regulated in part by calcium, via calmodulin kinase II, as well as the conserved protein TIR-1. PMK-1 and PMK-2 act redundantly downstream of TIR-1/NSY-1/SEK-1 to induce TPH-1 expression in the ADF neuron following exposure to bacteria. Genes pmk-1 and pmk-2 function redundantly during olfactory neuronal development. Activation of PMK-1 following arsenite treatment is dependent on SEK-1 but independent of NSY-1, differing from the NSY-1/SEK-1/PMK-1 cascade used during infection and osmotic stress. Unique upstream components activating PMK-1 induce SKN-1 activation following toxin and bacterial exposure
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + GLH-1
ADP + phosphorylated GLH-1
show the reaction diagram
-
-
-
?
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + GLH-1
ADP + phosphorylated GLH-1
show the reaction diagram
H2KZI0, O44408, O44514, Q17446, Q8MXI4
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-
-
?
additional information
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
arsenite
treatment of worms with arsenite, a toxic ROS-producing compound, induces a robust phosphorylation of PMK-1, induction of oxidative stress-responsive genes, and eventual lethality. Activation of PMK-1 following arsenite treatment is dependent on SEK-1 but independent of NSY-1, differing from the NSY-1/SEK-1/PMK-1 cascade used during infection and osmotic stress
additional information
-
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
15 - 20
rise of degree of phosphorylation of isoforms JNK-1alpha and JNK-1beta
additional information
ambient temperature of 1-37°C specifically influences the activation/phosphorylation of the MAPkinase JNK-1
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
1 - 37
degree of phosphorylation of isoforms JNK-1alpha and JNK-1beta increase with ambient temperature
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
; the enzyme is expressed in neuronal tissue; the enzyme is expressed in neuronal tissue
Manually annotated by BRENDA team
activated JNK-1 observed only in neuronal cells; JNK-1 is specific for neuronal cells
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
analysis
the use of 3'-UTR elements to regulate tissue-specific expression of pmk-2 provides a mechanism that endows context specificity to p38 paralogues
additional information
indirect interactions between neuronal MAPK and peripheral insulin-like signaling in response to environmental stimuli (temperature, H2O2)