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Literature summary for 2.7.11.24 extracted from
- Context specificity of stress-activated mitogen-activated protein (MAP) kinase signaling: the story as told by Caenorhabditis elegans (2016), J. Biol. Chem., 291, 7796-7804.
Activating Compound
| Activating Compound | Comment | Organism | Structure |
|---|---|---|---|
| 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 | Caenorhabditis elegans |  |
| additional information | C493C.10 is phosphorylated and activated by mitogen-activated protein kinase kinase sek-5 | Caenorhabditis elegans | |
| additional information | jnk-1 is phosphorylated and activated by mitogen-activated protein kinase kinase sek-4. Activation of JNK signaling occurs under conditions of heavy metal stress | Caenorhabditis elegans | |
| additional information | kgb-1 is phosphorylated and activated by mitogen-activated protein kinase kinase jkk-1 | Caenorhabditis elegans | |
| additional information | kgb-2 is phosphorylated and activated by mitogen-activated protein kinase kinase sek-3 | Caenorhabditis elegans | |
| additional information | pmk-1 is phosphorylated and activated by mitogen-activated protein kinase kinase mkk-4. Unique upstream components activating PMK-1 induce SKN-1 activation following toxin and bacterial exposure | Caenorhabditis elegans | |
| additional information | pmk-2 is phosphorylated and activated by mitogen-activated protein kinase kinase sek-1 | Caenorhabditis elegans | |
| additional information | pmk-3 is phosphorylated and activated by mitogen-activated protein kinase kinase mek-1 | Caenorhabditis elegans |
Application
| Application | Comment | Organism |
|---|---|---|
| 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 | Caenorhabditis elegans |
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| additional information | a kgb-1 null mutant is obtained by targeted deletion | Caenorhabditis elegans |
| additional information | a strain with mutations in both pmk-1 and pmk-2 is serendipitously identified in a screen searching for suppressors of the pmk-1 loss of function phenotype following bacterial infection | Caenorhabditis elegans |
| additional information | a strain with mutations in both pmk-1 and pmk-2 is serendipitously identified in a screen searching for suppressors of the pmk-1 loss of function phenotype following bacterial infection. 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 | Caenorhabditis elegans |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| synapse | - |
Caenorhabditis elegans | 45202 | - |
Metals/Ions
| Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|
| Mg2+ | required | Caenorhabditis elegans | |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP + GLH-1 | Caenorhabditis elegans | - |
ADP + phosphorylated GLH-1 | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Caenorhabditis elegans | - |
- |
- |
| Caenorhabditis elegans | H2KZI0 | - |
- |
| Caenorhabditis elegans | O44408 | - |
- |
| Caenorhabditis elegans | O44514 | - |
- |
| Caenorhabditis elegans | Q17446 | - |
- |
| Caenorhabditis elegans | Q8MXI4 | - |
- |
| Caenorhabditis elegans | Q8WQG9 | - |
- |
Posttranslational Modification
| Posttranslational Modification | Comment | Organism |
|---|---|---|
| phosphoprotein | C493C.10 is phosphorylated and activated by mitogen-activated protein kinase kinase sek-5 | Caenorhabditis elegans |
| phosphoprotein | jnk-1 is phosphorylated and activated by mitogen-activated protein kinase kinase sek-4 | Caenorhabditis elegans |
| phosphoprotein | kgb-1 is phosphorylated and activated by mitogen-activated protein kinase kinase jkk-1 | Caenorhabditis elegans |
| phosphoprotein | kgb-2 is phosphorylated and activated by mitogen-activated protein kinase kinase sek-3 | Caenorhabditis elegans |
| phosphoprotein | pmk-1 is phosphorylated and activated by mitogen-activated protein kinase kinase mkk-4. 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 | Caenorhabditis elegans |
| phosphoprotein | pmk-2 is phosphorylated and activated by mitogen-activated protein kinase kinase sek-1 | Caenorhabditis elegans |
| phosphoprotein | pmk-3 is phosphorylated and activated by mitogen-activated protein kinase kinase mek-1 | Caenorhabditis elegans |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| germ cell | - |
Caenorhabditis elegans | - |
| intestine | - |
Caenorhabditis elegans | - |
| additional information | the enzyme shows a broad tissue expression pattern | Caenorhabditis elegans | - |
| neuron | - |
Caenorhabditis elegans | - |
| neuron | the enzyme is expressed in neuronal tissue | Caenorhabditis elegans | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP + GLH-1 | - |
Caenorhabditis elegans | ADP + phosphorylated GLH-1 | - |
? | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| C493C.10 | - |
Caenorhabditis elegans |
| C493C.10 | gene and protein name | Caenorhabditis elegans |
| JNK-1 | - |
Caenorhabditis elegans |
| kgb-1 | - |
Caenorhabditis elegans |
| kgb-1 | kinase and GLH-binding | Caenorhabditis elegans |
| kgb-2 | - |
Caenorhabditis elegans |
| MAP kinase | - |
Caenorhabditis elegans |
| MAPK | - |
Caenorhabditis elegans |
| pmk-1 | - |
Caenorhabditis elegans |
| pmk-2 | - |
Caenorhabditis elegans |
| pmk-3 | - |
Caenorhabditis elegans |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| ATP | - |
Caenorhabditis elegans | |
General Information
| General Information | Comment | Organism |
|---|---|---|
| evolution | C493C.10 is an orthologue of mammalian JNK | Caenorhabditis elegans |
| evolution | jnk-1 is an orthologue of mammalian JNK | Caenorhabditis elegans |
| evolution | kgb-1 is an orthologue of mammalian JNK | Caenorhabditis elegans |
| evolution | kgb-2 is an orthologue of mammalian JNK. The JNK homologue KGB-2 shows 84% identity with KGB-1 | Caenorhabditis elegans |
| evolution | 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 | Caenorhabditis elegans |
| evolution | 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 | Caenorhabditis elegans |
| evolution | 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 | Caenorhabditis elegans |
| 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 | Caenorhabditis elegans |
| malfunction | 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 | Caenorhabditis elegans |
| malfunction | 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 | Caenorhabditis elegans |
| metabolism | distinct p38 and JNK MAPK cascades regulate a diverse class of normal biological processes during development and nervous system function | Caenorhabditis elegans |
| metabolism | the core MAPK signaling cassette consists of a MAPKKK/MAPKK/MAPK cascade, stress-activated MAPK components involved in non-stress-associated processes, overview | Caenorhabditis elegans |
| metabolism | 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 | Caenorhabditis elegans |
| metabolism | 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 | Caenorhabditis elegans |
| metabolism | 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 | Caenorhabditis elegans |
| 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 | Caenorhabditis elegans |
| physiological function | 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 | Caenorhabditis elegans |
| physiological function | roles for KGB-2 are in excess carbon dioxide (hypercapnia)-induced fertility defects and a slight negative role in axon injury response | Caenorhabditis elegans |
| physiological function | 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 | Caenorhabditis elegans |
| physiological function | 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 | Caenorhabditis elegans |
| physiological function | 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 | Caenorhabditis elegans |
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