MEK-2 is the C. elegans dual-specificity MAP kinase kinase in the Ras/Raf/ERK signaling module. It acts downstream of LET-60/Ras and LIN-45/Raf and upstream of SUR-1/MPK-1/ERK to phosphorylate and activate ERK-family MAP kinase during vulval induction and other Ras/MAPK outputs, and it is reused in the ERK-dependent response to Microbacterium nematophilum infection. The same LET-60/MEK-2/MPK-1 cascade is required in the germline for oocyte exit from pachytene, and RNAi of mek-2 shortens adult lifespan, consistent with ERK signalling promoting longevity through SKN-1 and DAF-16.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000165 MAPK cascade | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT correctly places MEK-2 in the conserved MAPK cascade. Reason: MEK-2 is the worm MEK/MAP2K in the Ras-Raf-MEK-ERK relay. Direct biochemical and genetic evidence showed that MEK-2 has MAP kinase kinase activity and acts between LIN-45/Raf and SUR-1/MPK-1, so the PAINT MAPK cascade inference is consistent with the C. elegans evidence and the conserved animal MAP2K role. Supporting Evidence: PMID:7729690 mek-2 acts between lin-45 raf and sur-1/mpk-1 in a signal transduction pathway |
| GO:0000165 MAPK cascade | IEA GO_REF:0000117 | ACCEPT | Summary: The ARBA MAPK cascade call matches the experimentally supported MEK-2 role in ERK MAPK signaling. Reason: Although this row is computational, it asserts the core pathway in which MEK-2 transduces Ras/Raf signals to MPK-1/ERK; the same MAPK cascade placement is supported by the MEK-2 cloning and infection studies. Supporting Evidence: PMID:7729690 The C. elegans MEK-2 protein can phosphorylate and activate a human MAP kinase |
| GO:0000165 MAPK cascade | IMP PMID:15268855 The ERK MAP kinase cascade mediates tail swelling and a prot... | ACCEPT | Summary: The ERK MAPK cascade row is supported by MEK-2 pathway activity during the rectal response to M. nematophilum infection. Reason: Nicholas and Hodgkin showed that rectal infection by the Gram-positive bacterium M. nematophilum uses an ERK MAPK cascade. This in vivo pathogen-response deployment is the same core LIN-45/MEK-2/MPK-1 cassette, so MAPK cascade is a correct direct pathway annotation. Supporting Evidence: PMID:15268855 an extracellular signal-regulated kinase (ERK) mitogen-activated protein (MAP) kinase cascade mediates tail swelling |
| GO:0004672 protein kinase activity | IEA GO_REF:0000002 | MODIFY | Summary: MEK-2 is a protein kinase, but MAP kinase kinase activity is the informative term for this protein. Reason: The InterPro kinase signature supports catalytic kinase activity, and direct MEK-2 biochemistry establishes the more specific MAP kinase kinase activity. Replace the broad parent protein kinase term with the existing GO:0004708 term. Proposed replacements: MAP kinase kinase activity Supporting Evidence: PMID:7729690 The C. elegans MEK-2 protein can phosphorylate and activate a human MAP kinase |
| GO:0004708 MAP kinase kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT correctly infers the conserved MEK/MAP2K catalytic activity. Reason: MEK-2 is a STE-family MAP kinase kinase, and both direct biochemistry and the conserved PAINT node support the same immediate MAPK phosphorylation activity. No target-specific loss or divergence is evident. Supporting Evidence: PMID:7729690 demonstrated that the MEK-2 protein possesses the biochemical properties of MAP kinase kinases |
| GO:0004708 MAP kinase kinase activity | IEA GO_REF:0000003 | ACCEPT | Summary: The EC-to-GO mapping correctly captures MEK-2 MAP kinase kinase activity. Reason: UniProt assigns MEK-2 to EC 2.7.12.2 for the dual-specificity MAP2K reactions, and the EC mapping to GO:0004708 matches the direct biochemical evidence that MEK-2 phosphorylates and activates MAP kinase. Supporting Evidence: PMID:7729690 The C. elegans MEK-2 protein can phosphorylate and activate a human MAP kinase |
| GO:0004712 protein serine/threonine/tyrosine kinase activity | IDA PMID:7729690 MEK-2, a Caenorhabditis elegans MAP kinase kinase, functions... | MODIFY | Summary: The direct kinase assay supports MEK-2 catalysis, but the specific activity is MAP kinase kinase activity. Reason: The PMID:7729690 IDA evidence showed dual-specificity MEK/MAP2K behavior. GO:0004712 is true but too broad for the curated assertion; GO:0004708 names the specific MAP kinase kinase activity demonstrated for MEK-2. Proposed replacements: MAP kinase kinase activity Supporting Evidence: PMID:7729690 demonstrated that the MEK-2 protein possesses the biochemical properties of MAP kinase kinases |
| GO:0004712 protein serine/threonine/tyrosine kinase activity | IEA GO_REF:0000117 | MODIFY | Summary: MEK-2 is a dual-specificity kinase, but MAP kinase kinase activity is the better term. Reason: The ARBA protein serine/threonine/tyrosine kinase call is compatible with MEK-2 chemistry, but it does not capture the physiological MAPK substrate class. The more specific MAP kinase kinase term should be used. Proposed replacements: MAP kinase kinase activity Supporting Evidence: PMID:7729690 The C. elegans MEK-2 protein can phosphorylate and activate a human MAP kinase |
| GO:0004713 protein tyrosine kinase activity | IEA GO_REF:0000116 | MODIFY | Summary: The Rhea tyrosyl-protein phosphorylation half-reaction is part of the dual-specificity MAP2K chemistry, but the standalone tyrosine kinase term is too broad. Reason: MEK-2 phosphorylates MAP kinases as a dual-specificity MAP kinase kinase. A generic protein tyrosine kinase annotation loses that substrate specificity, so GO:0004708 is the appropriate replacement. Proposed replacements: MAP kinase kinase activity Supporting Evidence: PMID:7729690 MEK-2 protein possesses the biochemical properties of MAP kinase kinases |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: MEK-2 has the ATP-binding kinase fold, but ATP binding is an uninformative subfunction relative to MAP kinase kinase activity. Reason: The protein kinase domain includes predicted ATP-binding residues and ATP is the phosphate donor for MEK-2 catalysis. This row is mechanistically true, but it is a generic nucleotide-binding feature of the kinase fold rather than the core MAP2K activity itself. Supporting Evidence: file:worm/mek-2/mek-2-uniprot.txt FT BINDING 79..87 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" |
| GO:0006950 response to stress | IEA GO_REF:0000117 | TOO GENERAL | Summary: The ARBA stress-response parent is too generic and duplicates a manually curated pathogen-defense row. Reason: True but uninformative: defense response to Gram-positive bacterium, kept in this review on experimental evidence, entails response to stress. That pathogen-specific row carries the supported MEK-2 stress role. Supporting Evidence: PMID:15268855 Involvement in pathogen defense represents a new role for ERK MAP kinase signaling in this organism. |
| GO:0007265 Ras protein signal transduction | IGI PMID:11861555 Caenorhabditis elegans lin-45 raf is essential for larval vi... | ACCEPT | Summary: MEK-2 functions downstream of LET-60/Ras in Ras protein signal transduction. Reason: The genetic evidence places MEK-2 in the LET-60/Ras-mediated Ras-Raf-MEK-ERK pathway. Because MEK-2 executes the kinase step that propagates the Ras/Raf signal to MPK-1/ERK, this is a direct pathway annotation rather than a terminal developmental readout. Supporting Evidence: PMID:11861555 LIN-45, MEK-2, and MPK-1 ERK MAP kinase function in a predominantly linear signaling pathway |
| GO:0040025 vulval development | IGI PMID:11861555 Caenorhabditis elegans lin-45 raf is essential for larval vi... | KEEP AS NON CORE | Summary: MEK-2 contributes to LET-60/LIN-45-dependent vulval induction, a non-core developmental output of ERK signaling. Reason: The LIN-45 study supports a linear LET-60/Ras to LIN-45/Raf to MEK-2 to MPK-1/ERK module that induces vulval fates. Vulval development is a valid in vivo output, but it is organismal and context-specific relative to MEK-2's reusable MAP kinase kinase activity. Supporting Evidence: PMID:11861555 The lin-45(null) phenotype is similar to the mek-2(null) and mpk-1(null) phenotypes |
| GO:0040025 vulval development | IGI PMID:11861555 Caenorhabditis elegans lin-45 raf is essential for larval vi... | KEEP AS NON CORE | Summary: MEK-2 is required in the Ras/Raf/ERK relay that patterns vulval precursor cells. Reason: The genetic interaction row is compatible with the evidence that LIN-45, MEK-2, and MPK-1 act together in vulval cell fate induction. Retain it as a non-core developmental output of the core MAP2K relay. Supporting Evidence: PMID:11861555 lin-45 is essential for larval viability, fertility, and the induction of vulval cell fates |
| GO:0040025 vulval development | IGI PMID:11861555 Caenorhabditis elegans lin-45 raf is essential for larval vi... | KEEP AS NON CORE | Summary: MEK-2 participates in the ERK module that drives vulval development. Reason: The severe LIN-45/Raf phenotypes resembled mek-2 and mpk-1 null phenotypes, placing MEK-2 in the MAPK cassette required for vulval induction. This row is sound but non-core because vulval development is a worm-specific developmental deployment. Supporting Evidence: PMID:11861555 LIN-45, MEK-2, and MPK-1 ERK MAP kinase function in a predominantly linear signaling pathway |
| GO:0040025 vulval development | IGI PMID:11861555 Caenorhabditis elegans lin-45 raf is essential for larval vi... | KEEP AS NON CORE | Summary: MEK-2 genetically supports vulval cell fate induction through the LET-60/LIN-45/MPK-1 ERK pathway. Reason: The WormBase IGI row is consistent with MEK-2 being the MEK kinase in the Ras/Raf/ERK module required for vulval induction. The biological process should be kept, but as a non-core developmental consequence of the signaling relay. Supporting Evidence: PMID:7729690 The mek-2 gene plays a key role in the let-60 ras-mediated vulval induction pathway |
| GO:0050830 defense response to Gram-positive bacterium | IMP PMID:15268855 The ERK MAP kinase cascade mediates tail swelling and a prot... | KEEP AS NON CORE | Summary: MEK-2 signaling contributes to defense against the Gram-positive bacterium M. nematophilum. Reason: The ERK MAPK cassette mediates tail swelling and protection from severe constipation during rectal M. nematophilum infection. That is a real physiological use of MEK-2 signaling, but it is a pathogen-specific downstream deployment rather than the core MAP2K activity. Supporting Evidence: PMID:15268855 protects C. elegans from severe constipation |
| GO:0097110 scaffold protein binding | IPI PMID:10409742 Kinase suppressor of Ras forms a multiprotein signaling comp... | KEEP AS NON CORE | Summary: MEK-2 binds the Ras-pathway scaffold KSR-1. Reason: The KSR study showed that nematode KSR proteins can bind MEKs and that KSR-MEK binding changes MEK localization, supporting the MEK-2 to KSR-1 scaffold-binding row. This interaction is pathway-relevant but ancillary to the core MAP kinase kinase activity. Supporting Evidence: PMID:10409742 Both nematode and mammalian KSRs are capable of binding to MEKs |
| GO:0106310 protein serine kinase activity | IEA GO_REF:0000116 | MODIFY | Summary: The Rhea serine-phosphorylation half-reaction is a broad representation of MEK-2 dual-specificity kinase chemistry. Reason: Rhea maps EC 2.7.12.2 to generic protein serine kinase activity, but MEK-2's specific role is MAP kinase kinase activity in the ERK cascade. Use the substrate-specific MAP2K term instead of the single-residue-class parent. Proposed replacements: MAP kinase kinase activity Supporting Evidence: PMID:7729690 MEK-2 protein possesses the biochemical properties of MAP kinase kinases |
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Download this section (compressed HTML)mek-2 encodes a MAP kinase kinase; MEK-2 functions as a core component of Ras-mediated signal transduction pathways that regulate several biological processes including larval development, vulval development, cell migration, meiotic cell cycle progression, olfaction, and pathogen defense.
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