PMK-1 is the C. elegans ortholog of mammalian p38 MAPK, functioning as a central stress-activated protein kinase in innate immunity and oxidative stress response. It operates within the conserved TIR-1-NSY-1-SEK-1-PMK-1 signaling cascade, where it is activated by dual phosphorylation on Thr-191 and Tyr-193 by the upstream MAPKK SEK-1. PMK-1 phosphorylates key transcription factors including SKN-1 (triggering its nuclear translocation during oxidative stress) and ATF-7 (converting it from a repressor to an activator of immune effector genes). The kinase is essential for defense against Gram-negative and Gram-positive bacteria, fungal pathogens, and various environmental stresses including osmotic stress and reactive oxygen species.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004674 protein serine/threonine kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PMK-1 is a well-established serine/threonine kinase as demonstrated by direct enzymatic assays. The IBA annotation is supported by extensive experimental evidence showing PMK-1 phosphorylates substrates including SKN-1 and ATF-7 [PMID:16166371, PMID:20369020]. Reason: Core molecular function of PMK-1. Direct kinase activity has been demonstrated in multiple studies showing phosphorylation of transcription factors SKN-1 and ATF-7 [PMID:16166371, PMID:20369020]. Supporting Evidence: PMID:16166371 In response to oxidative stress, PMK-1 phosphorylates SKN-1, leading to its accumulation in intestine nuclei PMID:20369020 ATF-7 functions as a repressor of PMK-1-regulated genes that undergoes a switch to an activator upon phosphorylation by PMK-1 file:worm/pmk-1/pmk-1-deep-research-falcon.md model: Edison Scientific Literature |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: Nuclear localization of PMK-1 is supported by IDA evidence showing it localizes to the nucleus under certain conditions. Reason: Nuclear localization is supported by IDA evidence from multiple publications and is consistent with PMK-1's role in phosphorylating nuclear transcription factors. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: Cytoplasmic localization is consistent with PMK-1 being a MAP kinase that shuttles between cytoplasm and nucleus. Reason: MAP kinases typically reside in the cytoplasm under basal conditions and translocate to the nucleus upon activation. Supported by IDA experimental evidence. |
| GO:0035556 intracellular signal transduction | IBA GO_REF:0000033 | ACCEPT | Summary: PMK-1 is a core component of the p38 MAPK signaling cascade, functioning as the terminal kinase in the NSY-1-SEK-1-PMK-1 pathway [PMID:12142542, PMID:11703092]. Reason: This is a fundamental aspect of PMK-1 function. It receives signals from upstream kinases and transmits them to downstream effectors. Supporting Evidence: PMID:12142542 a p38 ortholog, pmk-1, functions as the downstream MAP kinase required for pathogen defense PMID:11703092 An active form of MAPK/ERK kinase 6 (MEK6) phosphorylated and activated recombinant PMK-1 |
| GO:0000166 nucleotide binding | IEA GO_REF:0000043 | ACCEPT | Summary: As a kinase, PMK-1 requires ATP binding for its catalytic activity. This is a parent term of ATP binding which is more specific. Reason: Valid IEA annotation based on keyword mapping. All kinases bind nucleotides (specifically ATP). More specific annotation GO:0005524 (ATP binding) is also present. |
| GO:0000302 response to reactive oxygen species | IEA GO_REF:0000117 | ACCEPT | Summary: PMK-1 is activated by oxidative stress and phosphorylates SKN-1 to regulate the oxidative stress response [PMID:16166371]. This IEA annotation is supported by IEP experimental evidence. Reason: Supported by experimental evidence showing PMK-1 phosphorylation increases in response to ROS and regulates SKN-1-mediated detoxification gene expression. Supporting Evidence: PMID:16166371 Here we show that the Caenorhabditis elegans PMK-1 p38 MAPK pathway regulates the oxidative stress response via the CNC transcription factor SKN-1 |
| GO:0004672 protein kinase activity | IEA GO_REF:0000002 | ACCEPT | Summary: Parent term of protein serine/threonine kinase activity. Valid but redundant given more specific IDA-supported annotations. Reason: Accurate parent term annotation. PMK-1 has well-established protein kinase activity confirmed by IDA evidence. |
| GO:0004674 protein serine/threonine kinase activity | IEA GO_REF:0000043 | ACCEPT | Summary: Duplicate of IBA annotation above. Valid IEA based on UniProt keyword mapping. Reason: Core molecular function supported by multiple lines of evidence including IDA annotations. |
| GO:0004707 MAP kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: PMK-1 is explicitly identified as a p38 MAP kinase. This is the most specific and appropriate molecular function term for this enzyme [PMID:11703092, PMID:12142542, PMID:16166371]. Reason: This is the core molecular function of PMK-1. It is a p38 MAP kinase with extensive experimental validation. Supporting Evidence: PMID:11703092 we isolated cDNAs encoding three kinases, PMK-1, PMK-2, and PMK-3, which we call p38 map kinases due to their high sequence identity with p38 |
| GO:0005524 ATP binding | IEA GO_REF:0000120 | ACCEPT | Summary: ATP binding is essential for kinase activity. Supported by protein domain analysis showing ATP binding site. Reason: Required for kinase catalytic activity. UniProt entry shows ATP binding residues in the kinase domain. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: Duplicate of IBA annotation. Nuclear localization is well-supported by experimental evidence. Reason: Valid annotation supported by IDA evidence from multiple studies. |
| GO:0005737 cytoplasm | IEA GO_REF:0000117 | ACCEPT | Summary: Duplicate of IBA annotation. Cytoplasmic localization is expected for a MAP kinase. Reason: Valid annotation consistent with MAP kinase biology. |
| GO:0006955 immune response | IEA GO_REF:0000117 | ACCEPT | Summary: PMK-1 is a central regulator of innate immunity in C. elegans. This general term is accurate but more specific terms like "innate immune response" and "antibacterial innate immune response" are also annotated. Reason: Core biological function of PMK-1. It regulates innate immunity against bacterial and fungal pathogens. Supporting Evidence: PMID:12142542 a p38 ortholog, pmk-1, functions as the downstream MAP kinase required for pathogen defense |
| GO:0006970 response to osmotic stress | IEA GO_REF:0000117 | ACCEPT | Summary: PMK-1 is activated by osmotic stress, consistent with its role as a stress-activated kinase [PMID:11703092]. Reason: Supported by IDA evidence showing PMK-1 activation in response to osmotic stress. Supporting Evidence: PMID:11703092 When transfected into mammalian cells, these kinases, like p38, are stimulated by osmotic stresses |
| GO:0007165 signal transduction | IEA GO_REF:0000117 | ACCEPT | Summary: Parent term of intracellular signal transduction. Valid but less specific than the IBA-annotated term. Reason: Accurate general term for PMK-1 function in MAPK signaling. |
| GO:0009408 response to heat | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Heat stress response is a pleiotropic function of stress-activated kinases. Supported by IMP evidence [PMID:22125500]. Reason: While PMK-1 does respond to heat stress, this is not its primary function. It represents a secondary stress response pathway. |
| GO:0016301 kinase activity | IEA GO_REF:0000043 | ACCEPT | Summary: Very general parent term of protein kinase activity. Valid but highly redundant with more specific annotations. Reason: Accurate parent term. PMK-1 is unambiguously a kinase. |
| GO:0016740 transferase activity | IEA GO_REF:0000043 | ACCEPT | Summary: Very general parent term. Kinases are transferases that transfer phosphate groups. Reason: Accurate but very general. More specific annotations are present. |
| GO:0042742 defense response to bacterium | IEA GO_REF:0000117 | ACCEPT | Summary: PMK-1 is essential for defense against both Gram-negative and Gram-positive bacteria. More specific child terms are also annotated with IMP evidence. Reason: Core function of PMK-1 in innate immunity. Extensively validated by experimental evidence. Supporting Evidence: PMID:12142542 a p38 ortholog, pmk-1, functions as the downstream MAP kinase required for pathogen defense |
| GO:0046872 metal ion binding | IEA GO_REF:0000043 | ACCEPT | Summary: PMK-1 requires Mg2+ or Mn2+ as cofactors for catalytic activity, as documented in UniProt. Reason: Required for kinase catalytic activity. UniProt annotation confirms requirement for divalent metal cations. |
| GO:0050832 defense response to fungus | IEA GO_REF:0000117 | ACCEPT | Summary: PMK-1 is required for defense against fungal pathogens including Drechmeria coniospora [PMID:18394898]. Reason: Well-supported by experimental evidence. PMK-1 is required for antifungal antimicrobial peptide expression. Supporting Evidence: PMID:18394898 a conserved p38-MAP kinase cascade is required in the epidermis for the response to both infection and wounding |
| GO:0071248 cellular response to metal ion | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: PMK-1 responds to heavy metals including cadmium and copper, with nuclear accumulation and downstream signaling [PMID:28632756]. Reason: Validated by IMP evidence but represents a secondary stress response function rather than core immune function. |
| GO:0080135 regulation of cellular response to stress | IEA GO_REF:0000117 | ACCEPT | Summary: PMK-1 is a master regulator of stress responses including oxidative stress, osmotic stress, and pathogen stress. Reason: Accurate characterization of PMK-1 function as a stress-activated kinase. |
| GO:0106310 protein serine kinase activity | IEA GO_REF:0000116 | ACCEPT | Summary: Based on Rhea reaction mapping for serine phosphorylation. PMK-1 does phosphorylate serine residues. Reason: Accurate annotation based on catalytic activity. PMK-1 phosphorylates serine residues on substrates like SKN-1. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:17888400 Caenorhabditis elegans pgp-5 is involved in resistance to ba... | ACCEPT | Summary: PMK-1 positively regulates transcription of immune effector genes through phosphorylation of transcription factors like ATF-7 and SKN-1. Reason: PMK-1 activates transcription of immune genes by phosphorylating ATF-7, converting it from a repressor to an activator [PMID:20369020]. Supporting Evidence: PMID:17888400 Caenorhabditis elegans pgp-5 is involved in resistance to bacterial infection and heavy metal and its regulation requires TIR-1 and a p38 map kinase cascade. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:30789901 Global transcriptional regulation of innate immunity by ATF-... | ACCEPT | Summary: Additional evidence for PMK-1 role in transcriptional regulation through ATF-7. Reason: Consistent with core function in regulating immune gene expression. Supporting Evidence: PMID:30789901 the PMK-1 p38 mitogen-activated protein kinase (MAPK) pathway regulates innate immunity of C. elegans through phosphorylation of the CREB/ATF bZIP transcription factor, ATF-7 |
| GO:0050829 defense response to Gram-negative bacterium | IMP PMID:17888400 Caenorhabditis elegans pgp-5 is involved in resistance to ba... | ACCEPT | Summary: PMK-1 is essential for defense against Gram-negative pathogens including P. aeruginosa [PMID:12142542]. Reason: Core immune function of PMK-1. Validated by multiple independent studies. Supporting Evidence: PMID:17888400 Caenorhabditis elegans pgp-5 is involved in resistance to bacterial infection and heavy metal and its regulation requires TIR-1 and a p38 map kinase cascade. |
| GO:0050829 defense response to Gram-negative bacterium | IMP PMID:30789901 Global transcriptional regulation of innate immunity by ATF-... | ACCEPT | Summary: Additional evidence for PMK-1 role in Gram-negative defense. Reason: Consistent with core immune function. Supporting Evidence: PMID:30789901 Genetic analysis of resistance of C. elegans to infection by pathogenic Pseudomonas aeruginosa has defined an essential role for a conserved p38 mitogen-activated protein kinase pathway |
| GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding | IPI PMID:20369020 Phosphorylation of the conserved transcription factor ATF-7 ... | ACCEPT | Summary: PMK-1 directly interacts with transcription factor ATF-7 to phosphorylate and regulate it [PMID:20369020]. Reason: Direct physical interaction with ATF-7 demonstrated by biochemical studies. Supporting Evidence: PMID:20369020 biochemical characterization of the interaction between ATF-7 and PMK-1 |
| GO:1902236 negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway | IMP PMID:21857923 Dysregulated LRRK2 signaling in response to endoplasmic reti... | KEEP AS NON CORE | Summary: PMK-1 protects against ER stress-induced apoptosis, representing a cytoprotective function in stress response. Reason: This is a secondary protective function of PMK-1 signaling, not its primary role in innate immunity. Supporting Evidence: PMID:21857923 Dysregulated LRRK2 signaling in response to endoplasmic reticulum stress leads to dopaminergic neuron degeneration in C. |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:16166371 The C. elegans p38 MAPK pathway regulates nuclear localizati... | ACCEPT | Summary: Direct enzymatic demonstration of PMK-1 kinase activity. This is the primary experimental evidence for the molecular function. Reason: Core molecular function with direct experimental evidence. PMK-1 was shown to phosphorylate SKN-1. Supporting Evidence: PMID:16166371 In response to oxidative stress, PMK-1 phosphorylates SKN-1, leading to its accumulation in intestine nuclei |
| GO:0050829 defense response to Gram-negative bacterium | IMP PMID:34804026 The bZIP Transcription Factor ZIP-11 Is Required for the Inn... | ACCEPT | Summary: Additional evidence for PMK-1 role in Gram-negative defense through ZIP-11 regulation. Reason: Consistent with core immune function. Supporting Evidence: PMID:34804026 intestinal ZIP-11 regulates innate immune response through constituting a feedback loop with the conserved PMK-1/p38 mitogen-activated protein signaling pathway |
| GO:0009408 response to heat | IMP PMID:22125500 Physiological IRE-1-XBP-1 and PEK-1 signaling in Caenorhabdi... | KEEP AS NON CORE | Summary: PMK-1 is involved in heat stress response as part of broader stress signaling network. Reason: Secondary stress response function. PMK-1 primary role is in innate immunity. Supporting Evidence: PMID:22125500 2011 Nov 17. Physiological IRE-1-XBP-1 and PEK-1 signaling in Caenorhabditis elegans larval development and immunity. |
| GO:0034976 response to endoplasmic reticulum stress | IMP PMID:22125500 Physiological IRE-1-XBP-1 and PEK-1 signaling in Caenorhabdi... | KEEP AS NON CORE | Summary: PMK-1 participates in ER stress response signaling. Reason: Part of broader stress response network but not a core function. Supporting Evidence: PMID:22125500 2011 Nov 17. Physiological IRE-1-XBP-1 and PEK-1 signaling in Caenorhabditis elegans larval development and immunity. |
| GO:0050829 defense response to Gram-negative bacterium | IMP PMID:20182512 An essential role for XBP-1 in host protection against immun... | ACCEPT | Summary: Evidence from XBP-1 study showing PMK-1 requirement for host defense. Reason: Consistent with core immune function. Supporting Evidence: PMID:20182512 An essential role for XBP-1 in host protection against immune activation in C. |
| GO:0006979 response to oxidative stress | IMP PMID:22308034 Stabilization of RNT-1 protein, runt-related transcription f... | ACCEPT | Summary: PMK-1 phosphorylates RNT-1 during oxidative stress, stabilizing this transcription factor in the intestine. Reason: Core function in oxidative stress response through SKN-1 and RNT-1 phosphorylation. Supporting Evidence: PMID:22308034 RNT-1 was phosphorylated by SEK-1/PMK-1 in vitro |
| GO:0005634 nucleus | IDA PMID:28632756 Identification of ATF-7 and the insulin signaling pathway in... | ACCEPT | Summary: Direct observation of PMK-1 nuclear localization, particularly in response to metal ions. Reason: Primary experimental evidence for subcellular localization. Supporting Evidence: PMID:28632756 eCollection 2017. Identification of ATF-7 and the insulin signaling pathway in the regulation of metallothionein in C. |
| GO:0071248 cellular response to metal ion | IMP PMID:28632756 Identification of ATF-7 and the insulin signaling pathway in... | KEEP AS NON CORE | Summary: PMK-1 is activated by heavy metals and regulates metallothionein expression through ATF-7. Reason: Secondary stress response function of the pathway. Supporting Evidence: PMID:28632756 eCollection 2017. Identification of ATF-7 and the insulin signaling pathway in the regulation of metallothionein in C. |
| GO:0004707 MAP kinase activity | IDA PMID:20369020 Phosphorylation of the conserved transcription factor ATF-7 ... | ACCEPT | Summary: Direct demonstration of MAP kinase activity through ATF-7 phosphorylation. Reason: Core molecular function with strong experimental evidence. Supporting Evidence: PMID:20369020 ATF-7 functions as a repressor of PMK-1-regulated genes that undergoes a switch to an activator upon phosphorylation by PMK-1 |
| GO:0140367 antibacterial innate immune response | IMP PMID:12142542 A conserved p38 MAP kinase pathway in Caenorhabditis elegans... | ACCEPT | Summary: PMK-1 is essential for antibacterial innate immunity. This is the landmark paper establishing PMK-1's role in innate immunity. Reason: This is the core biological function of PMK-1. The Kim et al. 2002 paper established the p38 MAPK pathway in C. elegans immunity. Supporting Evidence: PMID:12142542 a p38 ortholog, pmk-1, functions as the downstream MAP kinase required for pathogen defense |
| GO:0010628 positive regulation of gene expression | IMP PMID:22470487 The pseudokinase NIPI-4 is a novel regulator of antimicrobia... | ACCEPT | Summary: PMK-1 positively regulates antimicrobial peptide gene expression. Reason: Core function in regulating immune effector gene expression. Supporting Evidence: PMID:22470487 The induction of expression of the genes of the nlp-29 cluster is strongly dependent on the p38 MAPK pmk-1 |
| GO:0050832 defense response to fungus | IMP PMID:22470487 The pseudokinase NIPI-4 is a novel regulator of antimicrobia... | ACCEPT | Summary: PMK-1 is required for nlp-29 antimicrobial peptide induction after D. coniospora infection. Reason: Core immune function against fungal pathogens. Supporting Evidence: PMID:22470487 The induction of expression of the genes of the nlp-29 cluster is strongly dependent on the p38 MAPK pmk-1 |
| GO:1900182 positive regulation of protein localization to nucleus | IMP PMID:16166371 The C. elegans p38 MAPK pathway regulates nuclear localizati... | ACCEPT | Summary: PMK-1 phosphorylates SKN-1, promoting its nuclear localization during oxidative stress. Reason: Key mechanism by which PMK-1 activates the oxidative stress response. Supporting Evidence: PMID:16166371 In response to oxidative stress, PMK-1 phosphorylates SKN-1, leading to its accumulation in intestine nuclei |
| GO:0061760 antifungal innate immune response | IMP PMID:18394898 Distinct innate immune responses to infection and wounding i... | ACCEPT | Summary: PMK-1 is required for the epidermal immune response to fungal infection. Reason: Core immune function. PMK-1 is required for nlp-29 induction after D. coniospora infection. Supporting Evidence: PMID:18394898 a conserved p38-MAP kinase cascade is required in the epidermis for the response to both infection and wounding |
| GO:0050829 defense response to Gram-negative bacterium | IMP PMID:25274306 Mitochondrial UPR-regulated innate immunity provides resista... | ACCEPT | Summary: PMK-1 is required for defense against P. aeruginosa. Reason: Consistent with core immune function. Supporting Evidence: PMID:25274306 Mitochondrial UPR-regulated innate immunity provides resistance to pathogen infection. |
| GO:0050829 defense response to Gram-negative bacterium | IGI PMID:25274306 Mitochondrial UPR-regulated innate immunity provides resista... | ACCEPT | Summary: Genetic interaction evidence for PMK-1 role in defense. Reason: Supports core immune function. Supporting Evidence: PMID:25274306 Mitochondrial UPR-regulated innate immunity provides resistance to pathogen infection. |
| GO:0050830 defense response to Gram-positive bacterium | IMP PMID:24972867 Orthosiphon stamineus protects Caenorhabditis elegans agains... | ACCEPT | Summary: PMK-1 is required for defense against S. aureus and other Gram-positive bacteria. Reason: Core immune function. PMK-1 defends against both Gram-negative and Gram-positive bacteria. Supporting Evidence: PMID:24972867 Orthosiphon stamineus protects Caenorhabditis elegans against Staphylococcus aureus infection through immunomodulation. |
| GO:0004672 protein kinase activity | IDA PMID:20369020 Phosphorylation of the conserved transcription factor ATF-7 ... | ACCEPT | Summary: Direct demonstration of protein kinase activity. Reason: Core molecular function. Supporting Evidence: PMID:20369020 Phosphorylation of the conserved transcription factor ATF-7 by PMK-1 p38 MAPK regulates innate immunity in Caenorhabditis elegans. |
| GO:0050832 defense response to fungus | IMP PMID:18394898 Distinct innate immune responses to infection and wounding i... | ACCEPT | Summary: PMK-1 is required for epidermal immune response to D. coniospora. Reason: Core immune function. Supporting Evidence: PMID:18394898 a conserved p38-MAP kinase cascade is required in the epidermis for the response to both infection and wounding |
| GO:1900426 positive regulation of defense response to bacterium | IGI PMID:22554143 An age-dependent reversal in the protective capacities of JN... | ACCEPT | Summary: Genetic interaction showing PMK-1 positively regulates antibacterial defense. Reason: Core regulatory function in immunity. Supporting Evidence: PMID:22554143 2012 May 30. An age-dependent reversal in the protective capacities of JNK signaling shortens Caenorhabditis elegans lifespan. |
| GO:0093002 response to nematicide | IMP PMID:15256590 Mitogen-activated protein kinase pathways defend against bac... | KEEP AS NON CORE | Summary: PMK-1 provides defense against bacterial pore-forming toxins. Reason: Specialized stress response related to but distinct from core immune function. Supporting Evidence: PMID:15256590 Mitogen-activated protein kinase pathways defend against bacterial pore-forming toxins. |
| GO:0000165 MAPK cascade | IGI PMID:11751572 SEK-1 MAPKK mediates Ca2+ signaling to determine neuronal as... | ACCEPT | Summary: PMK-1 functions in a MAPK signaling cascade with NSY-1 and SEK-1. Reason: Core signaling function. PMK-1 is the terminal kinase in the NSY-1-SEK-1-PMK-1 cascade. Supporting Evidence: PMID:11751572 SEK-1 MAPKK mediates Ca2+ signaling to determine neuronal asymmetric development in Caenorhabditis elegans. |
| GO:0050829 defense response to Gram-negative bacterium | IMP PMID:17975555 A conserved Toll-like receptor is required for Caenorhabditi... | ACCEPT | Summary: Evidence from Toll-like receptor study showing PMK-1 requirement. Reason: Core immune function. Supporting Evidence: PMID:17975555 A conserved Toll-like receptor is required for Caenorhabditis elegans innate immunity. |
| GO:0050830 defense response to Gram-positive bacterium | IMP PMID:17975555 A conserved Toll-like receptor is required for Caenorhabditi... | ACCEPT | Summary: PMK-1 defends against Gram-positive bacteria. Reason: Core immune function. Supporting Evidence: PMID:17975555 A conserved Toll-like receptor is required for Caenorhabditis elegans innate immunity. |
| GO:0006970 response to osmotic stress | IDA PMID:11703092 Isolation and characterization of pmk-(1-3): three p38 homol... | ACCEPT | Summary: PMK-1 is activated by osmotic stress, like mammalian p38. Reason: Core stress-activated kinase function demonstrated in the original characterization paper. Supporting Evidence: PMID:11703092 When transfected into mammalian cells, these kinases, like p38, are stimulated by osmotic stresses |
| GO:0038066 p38MAPK cascade | IMP PMID:12142542 A conserved p38 MAP kinase pathway in Caenorhabditis elegans... | ACCEPT | Summary: PMK-1 is the p38 MAPK in the conserved p38 MAPK cascade. Reason: This is the most specific and accurate term for PMK-1's signaling pathway. Supporting Evidence: PMID:12142542 a p38 ortholog, pmk-1, functions as the downstream MAP kinase required for pathogen defense |
| GO:0050829 defense response to Gram-negative bacterium | IMP PMID:12142542 A conserved p38 MAP kinase pathway in Caenorhabditis elegans... | ACCEPT | Summary: Landmark paper establishing PMK-1 in P. aeruginosa defense. Reason: Core immune function from the seminal paper. Supporting Evidence: PMID:12142542 A genetic screen for Caenorhabditis elegans mutants with enhanced susceptibility to killing by Pseudomonas aeruginosa |
| GO:0038066 p38MAPK cascade | IEP PMID:16166371 The C. elegans p38 MAPK pathway regulates nuclear localizati... | ACCEPT | Summary: Expression pattern evidence for p38 MAPK cascade involvement. Reason: Supports core signaling function. Supporting Evidence: PMID:16166371 The C. elegans p38 MAPK pathway regulates nuclear localization of the transcription factor SKN-1 in oxidative stress response. |
| GO:0000302 response to reactive oxygen species | IEP PMID:16166371 The C. elegans p38 MAPK pathway regulates nuclear localizati... | ACCEPT | Summary: PMK-1 responds to oxidative stress by activating SKN-1. Reason: Core stress response function. Supporting Evidence: PMID:16166371 Here we show that the Caenorhabditis elegans PMK-1 p38 MAPK pathway regulates the oxidative stress response via the CNC transcription factor SKN-1 |
| GO:0000303 response to superoxide | IEP PMID:16166371 The C. elegans p38 MAPK pathway regulates nuclear localizati... | ACCEPT | Summary: PMK-1 responds to superoxide stress. Reason: Specific type of oxidative stress response. Supporting Evidence: PMID:16166371 The C. elegans p38 MAPK pathway regulates nuclear localization of the transcription factor SKN-1 in oxidative stress response. |
| GO:0004707 MAP kinase activity | IDA PMID:16166371 The C. elegans p38 MAPK pathway regulates nuclear localizati... | ACCEPT | Summary: Direct demonstration of MAP kinase activity. Reason: Core molecular function with strong experimental evidence. Supporting Evidence: PMID:16166371 The C. elegans p38 MAPK pathway regulates nuclear localization of the transcription factor SKN-1 in oxidative stress response. |
| GO:0018105 peptidyl-serine phosphorylation | IDA PMID:16166371 The C. elegans p38 MAPK pathway regulates nuclear localizati... | ACCEPT | Summary: PMK-1 phosphorylates serine residues on substrates. Reason: Direct demonstration of catalytic activity on serine residues. Supporting Evidence: PMID:16166371 The C. elegans p38 MAPK pathway regulates nuclear localization of the transcription factor SKN-1 in oxidative stress response. |
| GO:0006972 hyperosmotic response | IGI PMID:10393177 A Caenorhabditis elegans JNK signal transduction pathway reg... | ACCEPT | Summary: Genetic interaction evidence for hyperosmotic stress response. Reason: Part of stress-activated kinase function. Supporting Evidence: PMID:10393177 A Caenorhabditis elegans JNK signal transduction pathway regulates coordinated movement via type-D GABAergic motor neurons. |
| GO:0005634 nucleus | IDA PMID:20133945 A conserved PMK-1/p38 MAPK is required in caenorhabditis ele... | ACCEPT | Summary: Direct observation of nuclear localization during infection. Reason: Primary experimental evidence for localization. Supporting Evidence: PMID:20133945 2010 Feb 4. A conserved PMK-1/p38 MAPK is required in caenorhabditis elegans tissue-specific immune response to Yersinia pestis infection. |
| GO:0005829 cytosol | IDA PMID:20133945 A conserved PMK-1/p38 MAPK is required in caenorhabditis ele... | ACCEPT | Summary: Direct observation of cytosolic localization. Reason: Primary experimental evidence for localization. Supporting Evidence: PMID:20133945 2010 Feb 4. A conserved PMK-1/p38 MAPK is required in caenorhabditis elegans tissue-specific immune response to Yersinia pestis infection. |
| GO:0045087 innate immune response | IMP PMID:19454349 Conditioning protects C. elegans from lethal effects of ente... | ACCEPT | Summary: PMK-1 is required for innate immune response in conditioning protection. Reason: Core immune function. Supporting Evidence: PMID:19454349 Conditioning protects C. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:19454349 Conditioning protects C. elegans from lethal effects of ente... | ACCEPT | Summary: PMK-1 positively regulates immune gene transcription. Reason: Core regulatory function. Supporting Evidence: PMID:19454349 Conditioning protects C. |
| GO:0050829 defense response to Gram-negative bacterium | IMP PMID:19454349 Conditioning protects C. elegans from lethal effects of ente... | ACCEPT | Summary: Evidence for PMK-1 in EPEC defense. Reason: Core immune function. Supporting Evidence: PMID:19454349 Conditioning protects C. |
| GO:0004672 protein kinase activity | IDA PMID:11703092 Isolation and characterization of pmk-(1-3): three p38 homol... | ACCEPT | Summary: Original characterization demonstrating protein kinase activity. Reason: Primary experimental evidence from founding paper. Supporting Evidence: PMID:11703092 PMK-1 and PMK-2 phosphorylated activating transcription factor-2 (ATF-2), indicating an activity similar to mammalian p38 |
| GO:0012501 programmed cell death | IMP PMID:12526744 Caenorhabditis elegans innate immune response triggered by S... | KEEP AS NON CORE | Summary: PMK-1 may influence programmed cell death in immune context. Reason: Secondary function related to immune response but not core function. Supporting Evidence: PMID:12526744 Caenorhabditis elegans innate immune response triggered by Salmonella enterica requires intact LPS and is mediated by a MAPK signaling pathway. |
| GO:0045087 innate immune response | IMP PMID:12526744 Caenorhabditis elegans innate immune response triggered by S... | ACCEPT | Summary: PMK-1 is required for innate immunity against Salmonella. Reason: Core immune function. Supporting Evidence: PMID:12526744 Caenorhabditis elegans innate immune response triggered by Salmonella enterica requires intact LPS and is mediated by a MAPK signaling pathway. |
| GO:0004707 MAP kinase activity | IDA PMID:11703092 Isolation and characterization of pmk-(1-3): three p38 homol... | ACCEPT | Summary: Original demonstration of MAP kinase activity through ATF-2 phosphorylation. Reason: Core molecular function from founding paper. Supporting Evidence: PMID:11703092 PMK-1 and PMK-2 phosphorylated activating transcription factor-2 (ATF-2), indicating an activity similar to mammalian p38 |
| GO:0035556 intracellular signal transduction | IDA PMID:11703092 Isolation and characterization of pmk-(1-3): three p38 homol... | ACCEPT | Summary: PMK-1 functions in intracellular MAPK signaling. Reason: Core signaling function. Supporting Evidence: PMID:11703092 Isolation and characterization of pmk-(1-3): three p38 homologs in Caenorhabditis elegans. |
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Download this section (compressed HTML)Q: What are the specific phosphorylation sites on ATF-7 that are modified by PMK-1, and how does this affect ATF-7 DNA binding versus transcriptional activation domains?
Q: Are there tissue-specific differences in PMK-1 substrate specificity between intestinal and epidermal immunity?
Q: What is the mechanism by which PMK-1 distinguishes between different stress inputs (pathogen vs oxidative vs osmotic) to activate appropriate downstream responses?
Experiment: Phosphoproteomics analysis of PMK-1 activation to identify additional direct substrates beyond SKN-1 and ATF-7.
Experiment: ChIP-seq of ATF-7 in wild-type vs pmk-1 mutant backgrounds to comprehensively define PMK-1-regulated transcriptional programs.
Experiment: Live imaging of PMK-1 subcellular dynamics during pathogen infection vs oxidative stress to understand spatiotemporal regulation.
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