let-60 encodes the C. elegans Ras small GTPase that functions as a membrane-associated molecular switch downstream of receptor tyrosine kinases. SOS-1-mediated GTP loading activates LET-60, enabling interactions with effectors such as LIN-45/Raf and PLC-1 to control vulval induction, oogenesis, learning, and additional Ras-dependent developmental signals. Through the LIN-45/Raf-MEK-MPK-1 cascade, LET-60 also mediates LIN-3/LET-23 inductive signalling that sets anterior cell fates in male spicule development, acts within the sex myoblasts to control their final position during migration, and is required in mature olfactory neurons for efficient chemotaxis to odorants. FGF pathway signalling through EGL-15 and SEM-5 also restrains muscle membrane extension, a process in which LET-60 is implicated genetically.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0002119 nematode larval development | IGI PMID:11861555 Caenorhabditis elegans lin-45 raf is essential for larval vi... | KEEP AS NON CORE | Summary: LET-60/Ras contributes to LIN-45/Raf-dependent larval viability, but larval development is a downstream organismal output rather than the reusable Ras molecular role. Reason: LIN-45/Raf is activated downstream of LET-60/Ras and is required for larval viability, fertility, and vulval induction. The annotation is plausible for LET-60 in the RTK/Ras/MAPK pathway but is a broad developmental consequence, so it should be retained as non-core rather than treated as LET-60's core GTPase function. Supporting Evidence: PMID:11861555 Raf activation is initiated by an interaction with GTP-bound Ras |
| GO:0002119 nematode larval development | IMP PMID:11861555 Caenorhabditis elegans lin-45 raf is essential for larval vi... | KEEP AS NON CORE | Summary: LET-60/Ras contributes to LIN-45/Raf-dependent larval viability, but the larval-development term is broader than LET-60's core Ras switch activity. Reason: Severe lin-45 alleles phenocopy the downstream mek-2 and mpk-1 null defects in a pathway initiated by GTP-bound Ras. This supports a developmental requirement for the LET-60/Ras-to-LIN-45/Raf cascade, while the term itself is a pleiotropic non-core output. Supporting Evidence: PMID:11861555 Raf activation is initiated by an interaction with GTP-bound Ras |
| GO:0002119 nematode larval development | IMP PMID:21868609 Cell architecture: surrounding muscle cells shape gland cell... | UNDECIDED | Summary: The cached full text mentions a let-60 mutant strain in a pharyngeal-gland screen, but does not expose the LET-60-specific experiment behind this broad larval-development row. Reason: PMID:21868609 is a study of pharyngeal gland morphology and surrounding muscle architecture. Its cached full text lists let-60(sy101sy127) among strains used, but the visible results do not show why LET-60 should be asserted to execute nematode larval development, so this row should be revisited with the underlying WormBase curation context before keeping or removing it. |
| GO:0003924 GTPase activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: LET-60 is a conserved Ras-family small GTPase. Reason: LET-60 belongs to the Ras family and uses the canonical GTP-bound active/GDP-bound inactive switch cycle; the deep PAINT node for GTPase activity is consistent with direct LET-60 biochemical and genetic evidence and with the conserved function of animal Ras proteins. Supporting Evidence: PMID:21482356 RGEF-1b loads GTP onto LET-60 and RAP-1. |
| GO:0003924 GTPase activity | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO: the Ras-family domain correctly supports GTPase activity. Reason: IPR001806 is the small GTPase/Ras superfamily signature. LET-60 is the C. elegans Ras ortholog and the domain inference matches the experimentally observed LET-60 GTP/GDP switch. Supporting Evidence: PMID:21482356 RGEF-1b loads GTP onto LET-60 and RAP-1. |
| GO:0003924 GTPase activity | ISS PMID:9178006 Mechanism of activation of the Caenorhabditis elegans ras ho... | ACCEPT | Summary: ISS: LET-60 GTPase activity inferred from human H-Ras is valid. Reason: The ISS source is human HRAS, and LET-60 is a bona fide Ras-family protein. The temperature-sensitive LET-60 L19F allele was also modeled in human H-Ras and affected intrinsic GTP hydrolysis, reinforcing that the orthologous proteins share the same GTPase switch mechanism. Supporting Evidence: PMID:9178006 The ga89 mutation causes a leucine (L) to phenylalanine (F) substitution at amino acid 19, a residue conserved in all Ras proteins. |
| GO:0003925 G protein activity | IEA GO_REF:0000003 | ACCEPT | Summary: EC2GO: EC 3.6.5.2 maps appropriately to Ras-family G protein activity. Reason: GO:0003925 covers small monomeric GTPases as well as heterotrimeric G proteins; LET-60 is the worm Ras GTPase and UniProt assigns the corresponding EC 3.6.5.2 GTP phosphohydrolase activity. |
| GO:0005515 protein binding | IPI PMID:9674433 SUR-8, a conserved Ras-binding protein with leucine-rich rep... | REMOVE | Summary: IPI: LET-60 binds SUR-8/SOC-2, but generic protein binding loses the functional specificity of the Ras-effector interaction. Reason: The cited paper supports a direct SUR-8/Ras interaction and a positive SUR-8 role in Ras-mediated vulval signaling. GO:0005515 is nevertheless only a bare physical-interaction assertion, and this row should not be kept unless it can be curated to an evidence-backed, specific LET-60 molecular function. Supporting Evidence: PMID:9674433 SUR-8 protein interacts directly with Ras |
| GO:0005525 GTP binding | IDA PMID:21482356 A RasGRP, C. elegans RGEF-1b, couples external stimuli to be... | ACCEPT | Summary: LET-60 is GTP loaded by RGEF-1b in cells, directly supporting GTP binding by the Ras switch. Reason: The RGEF-1b study assayed active LET-60 by isolating LET-60-GTP with the immobilized RAF Ras-binding domain and showed that PMA-activated RGEF-1b increases cellular LET-60-GTP. GTP binding is therefore an experimentally supported core molecular function for LET-60. Supporting Evidence: PMID:21482356 RGEF-1b loads GTP onto LET-60 and RAP-1. |
| GO:0005525 GTP binding | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO: the Ras-family signatures correctly support GTP binding. Reason: The domain signatures identify LET-60 as a Ras-family nucleotide switch protein, and GTP binding is part of the canonical Ras biochemical cycle documented for LET-60 in RGEF-1b-mediated activation assays. Supporting Evidence: PMID:21482356 RGEF-1b loads GTP onto LET-60 and RAP-1. |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: plasma-membrane activity is conserved for the lipid-anchored LET-60/Ras GTPase. Reason: Ras proteins are membrane-tethered small GTPases, and UniProt describes LET-60 as cell-membrane localized through a lipid anchor. The PAINT placement of plasma-membrane activity on this Ras-family node is consistent with LET-60's core signaling mechanism. |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping: LET-60 is a lipid-anchored cell-membrane Ras protein. Reason: The electronic mapping from the reviewed UniProt subcellular location is consistent with LET-60's membrane-tethered Ras family biology and with the more specific plasma-membrane annotation on the same review. |
| GO:0005938 cell cortex | IDA PMID:16254074 Gene CATCHR--gene cloning and tagging for Caenorhabditis ele... | KEEP AS NON CORE | Summary: GFP::LET-60 was observed at the periphery/cortex of embryonic cells, a valid but secondary localization for this Ras GTPase. Reason: The Gene CATCHR localization study generated a GFP::LET-60 translational reporter and reported peripheral embryonic localization. That is compatible with membrane-proximal Ras signaling but is not as central as the plasma-membrane localization of the lipid-anchored switch. Supporting Evidence: PMID:16254074 GFP::LET-60 localizes, in part, to the periphery of cells in embryos |
| GO:0007165 signal transduction | IEA GO_REF:0000002 | MODIFY | Summary: The InterPro signal-transduction inference is correct but too broad for LET-60. Reason: LET-60 transduces receptor input as a Ras-family small GTPase, so the broad parent process GO:0007165 should be replaced by the existing and already independently supported Ras protein signal transduction term. Proposed replacements: Ras protein signal transduction |
| GO:0007173 epidermal growth factor receptor signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: LET-60 acts in the conserved LIN-3/LET-23 EGFR pathway. Reason: The PAINT node is grounded partly by C. elegans LET-60 itself and captures the conserved placement of Ras immediately downstream of EGFR-family receptors and upstream of Raf/MEK/ERK in vulval precursor cells. Supporting Evidence: PMID:2257629 increase in let-60 ras activity bypasses or reduces the need for upstream genes |
| GO:0007173 epidermal growth factor receptor signaling pathway | IGI PMID:2257629 let-60, a gene that specifies cell fates during C. elegans v... | ACCEPT | Summary: IGI: let-60 genetically specifies vulval precursor cell fates downstream of upstream vulval-induction genes. Reason: Han and Sternberg cloned let-60 as the Ras gene that mediates the switch between vulval and hypodermal fates; increased LET-60 Ras activity bypasses or reduces the requirement for upstream components of the LIN-3/LET-23 pathway. EGFR signaling is therefore a core C. elegans pathway context for LET-60. Supporting Evidence: PMID:2257629 increase in let-60 ras activity bypasses or reduces the need for upstream genes |
| GO:0007265 Ras protein signal transduction | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: Ras protein signal transduction is the central conserved biological role of LET-60. Reason: LET-60 is the worm Ras switch that is activated by receptor-coupled GEFs and then propagates signal to downstream effectors such as LIN-45, MEK-2, and MPK-1. The PAINT placement is at a deeply conserved Ras-family node and is fully consistent with LET-60 genetics and biochemistry. Supporting Evidence: PMID:21482356 RGEF-1b loads GTP onto LET-60 and RAP-1. |
| GO:0007517 muscle organ development | IGI PMID:16495308 FGF negatively regulates muscle membrane extension in Caenor... | UNDECIDED | Summary: The cached abstract supports an EGL-15/SEM-5 FGF pathway in body wall muscle-arm extension, but not the LET-60-specific experiment. Reason: PMID:16495308 is abstract-only locally. The visible abstract names the FGF ligand, FGFR, and SEM-5/GRB2 in regulation of muscle membrane extension, but it does not expose the exact LET-60 genetic interaction behind this WormBase IGI row, so this non-core developmental assertion needs curator follow-up. |
| GO:0007517 muscle organ development | IMP PMID:16495308 FGF negatively regulates muscle membrane extension in Caenor... | UNDECIDED | Summary: The cached abstract supports FGF-pathway control of muscle-arm extension, but does not show how LET-60 was perturbed. Reason: The muscle-organ-development assertion is plausible for an FGFR/SEM-5/Ras pathway context, but the PMID:16495308 cache is abstract-only and does not expose a LET-60-specific IMP experiment. Preserve the row for full-text follow-up rather than accepting or removing it from indirect pathway context. |
| GO:0007614 short-term memory | IGI PMID:26469632 Distinct roles of the RasGAP family proteins in C. elegans a... | KEEP AS NON CORE | Summary: LET-60 contributes to aversive olfactory short-term memory through RasGAP-regulated Ras signaling. Reason: RasGAP perturbations and the let-60(n2021) hypomorph place LET-60 in C. elegans associative learning and memory. This is a real neuronal output of Ras signaling, but it is more specialized than the core LET-60 GTPase switch function. Supporting Evidence: PMID:26469632 elegans Ras orthologue let-60 is involved in multiple processes during learning |
| GO:0007614 short-term memory | IGI PMID:26469632 Distinct roles of the RasGAP family proteins in C. elegans a... | KEEP AS NON CORE | Summary: LET-60 contributes to RasGAP-dependent short-term memory, but this is a neuronal behavioral output rather than the central Ras molecular activity. Reason: The RasGAP-family study found that gap mutants affect olfactory associative learning and short- and long-term memory, and that reduced let-60 activity restored rasgap-mutant learning and memory defects. Keep the term as a non-core Ras signaling output. Supporting Evidence: PMID:26469632 elegans Ras orthologue let-60 is involved in multiple processes during learning |
| GO:0008284 positive regulation of cell population proliferation | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA: Ras signaling can promote cell proliferation, but this is an output of the conserved pathway rather than LET-60 catalytic activity. Reason: The PAINT assertion is credible for animal Ras proteins that couple receptor signals to proliferative and differentiation responses. For C. elegans LET-60, this process is best retained as a non-core pathway outcome while the core annotation remains the GTPase activity that drives Ras protein signal transduction. |
| GO:0008306 associative learning | IGI PMID:26469632 Distinct roles of the RasGAP family proteins in C. elegans a... | KEEP AS NON CORE | Summary: LET-60 contributes to olfactory associative learning downstream of RasGAP control. Reason: The cited study used RasGAP mutants and let-60 hypomorph interactions to show that LET-60 participates in multiple stages of learning and memory. Associative learning is therefore a valid but neuron-specific output of LET-60 signaling, not the core Ras switch activity. Supporting Evidence: PMID:26469632 elegans Ras orthologue let-60 is involved in multiple processes during learning |
| GO:0016020 membrane | IEA GO_REF:0000002 | MODIFY | Summary: The InterPro membrane inference is sound but should be reported as plasma membrane for LET-60. Reason: LET-60 is a lipid-anchored Ras-family GTPase annotated to the plasma membrane by PAINT and UniProt subcellular-location mapping. The generic membrane parent term should be replaced by GO:0005886. Proposed replacements: plasma membrane |
| GO:0031344 regulation of cell projection organization | IGI PMID:16495308 FGF negatively regulates muscle membrane extension in Caenor... | UNDECIDED | Summary: The cached abstract supports FGF-pathway regulation of muscle membrane extension, but not this LET-60-specific genetic-interaction row. Reason: Regulation of muscle projections is a non-core plausible output of EGL-15/SEM-5/Ras signaling. However, PMID:16495308 is abstract-only in the local cache and the visible abstract does not show the LET-60 experiment or the supporting gene in this IGI row, so the assertion should be left for full-text verification. |
| GO:0031344 regulation of cell projection organization | IMP PMID:16495308 FGF negatively regulates muscle membrane extension in Caenor... | UNDECIDED | Summary: The cached PMID:16495308 abstract does not expose the LET-60-specific perturbation behind this muscle-projection row. Reason: The abstract describes FGF-pathway regulation of plasma-membrane extension from body-wall muscles but names LET-756, EGL-15, and SEM-5 rather than LET-60. Because the full text is not locally available, keep this IMP row undecided instead of second-guessing the WormBase curator. |
| GO:0040026 positive regulation of vulval development | IGI PMID:10409742 Kinase suppressor of Ras forms a multiprotein signaling comp... | KEEP AS NON CORE | Summary: LET-60 participates in KSR-dependent Ras/MAPK signaling that positively regulates vulval development. Reason: KSR-1 is a scaffold and positive regulator in the Ras/MAPK cascade downstream of LET-60; the genetic interaction captures a real vulval development output, but that developmental term is narrower and more organismal than the core LET-60 GTPase function. Supporting Evidence: PMID:10409742 KSR positively regulates Ras signaling |
| GO:0040026 positive regulation of vulval development | IGI PMID:11861555 Caenorhabditis elegans lin-45 raf is essential for larval vi... | KEEP AS NON CORE | Summary: LET-60 functions upstream of LIN-45/Raf to promote vulval induction. Reason: LIN-45/Raf functions in a predominantly linear Ras/Raf/MEK/ERK pathway and its Ras-binding and kinase-domain alleles perturb vulval induction. Vulval development is the canonical worm output of LET-60 EGFR/Ras/MAPK signaling, but it remains a species-specific developmental outcome rather than LET-60's core molecular function. Supporting Evidence: PMID:11861555 Raf activation is initiated by an interaction with GTP-bound Ras |
| GO:0040026 positive regulation of vulval development | IGI PMID:11861555 Caenorhabditis elegans lin-45 raf is essential for larval vi... | KEEP AS NON CORE | Summary: LET-60 genetically promotes vulval development through the LIN-45/Raf branch of the Ras/MAPK cascade. Reason: The LIN-45 study supports a Raf/MEK/ERK module downstream of LET-60/Ras for vulval cell fate induction. This row should be retained as a non-core developmental output of LET-60 signaling. Supporting Evidence: PMID:11861555 Raf activation is initiated by an interaction with GTP-bound Ras |
| GO:0040026 positive regulation of vulval development | IGI PMID:11861555 Caenorhabditis elegans lin-45 raf is essential for larval vi... | KEEP AS NON CORE | Summary: LET-60/Ras promotes vulval induction via LIN-45/Raf signaling. Reason: The severe lin-45 loss-of-function phenotype resembled mek-2 and mpk-1 null phenotypes, placing LIN-45 in the LET-60-dependent MAPK relay used for vulval induction. This is a biologically sound but downstream developmental annotation. Supporting Evidence: PMID:11861555 The lin-45(null) phenotype is similar to the mek-2(null) and mpk-1(null) phenotypes |
| GO:0040026 positive regulation of vulval development | IGI PMID:15455032 EGF signal propagation during C. elegans vulval development ... | KEEP AS NON CORE | Summary: LET-60 acts in ROM-1/LIN-3-dependent vulval signaling, a non-core developmental output of the Ras switch. Reason: ROM-1 extends LIN-3/EGF signaling among vulval precursor cells upstream of the LET-23/LET-60/MAPK cascade. The annotation captures a valid vulval-induction context while remaining downstream of LET-60's generic Ras GTPase activity. Supporting Evidence: PMID:15455032 ROM-1 relays the inductive AC signal from the proximal to the distal VPCs |
| GO:0040026 positive regulation of vulval development | IMP PMID:11861555 Caenorhabditis elegans lin-45 raf is essential for larval vi... | KEEP AS NON CORE | Summary: LIN-45/Raf genetic interactions support positive regulation of vulval development downstream of LET-60/Ras. Reason: The let-60/Raf/MEK/ERK relay is required for vulval precursor cells to adopt vulval fates, but positive regulation of vulval development is a nematode developmental output and should not be elevated over the core Ras GTPase activity. Supporting Evidence: PMID:11861555 Raf activation is initiated by an interaction with GTP-bound Ras |
| GO:0040028 regulation of vulval development | IGI PMID:28135265 Ξ²-Integrin de-phosphorylation by the Density-Enhanced Phosph... | KEEP AS NON CORE | Summary: LET-60 activity is modulated by DEP-1/PAT-3 cross-talk during vulval development. Reason: DEP-1 attenuates LET-23/EGFR signaling upstream of the LET-60/MAPK response and beta-integrin/talin mobility effects tune that vulval signaling network. Regulation of vulval development is valid in this context but is a pathway output rather than the LET-60 core function. Supporting Evidence: PMID:28135265 DEP-1 mediates binary cell fate decisions by negatively regulating EGFR signaling |
| GO:0040028 regulation of vulval development | IGI PMID:28135265 Ξ²-Integrin de-phosphorylation by the Density-Enhanced Phosph... | KEEP AS NON CORE | Summary: LET-60 participates in DEP-1-regulated vulval EGFR/Ras/MAPK signaling. Reason: The DEP-1/PAT-3 study analyzed a negative-feedback circuit that tunes LET-23 EGFR activity and therefore the downstream LET-60/MAPK vulval response. Keep this as a non-core developmental annotation for LET-60. Supporting Evidence: PMID:28135265 DEP-1 controls cell fate decisions by inhibiting the activation of the EGF receptor |
| GO:0040028 regulation of vulval development | IGI PMID:28135265 Ξ²-Integrin de-phosphorylation by the Density-Enhanced Phosph... | KEEP AS NON CORE | Summary: LET-60 acts in the DEP-1-modulated vulval EGFR/Ras/MAPK pathway. Reason: The cited genetic interactions concern regulators of LET-23/EGFR signal strength and the downstream Ras/MAPK cascade. This supports regulation of vulval development as a secondary biological-process output of LET-60. Supporting Evidence: PMID:28135265 DEP-1 controls cell fate decisions by inhibiting the activation of the EGF receptor |
| GO:0042659 regulation of cell fate specification | IMP PMID:9486792 The Hox gene lin-39 is required during C. elegans vulval ind... | KEEP AS NON CORE | Summary: LET-60/Ras signaling regulates the vulval cell-fate choice through LIN-39. Reason: The Hox gene lin-39 is required during vulval induction for Ras signaling to drive the correct cell-fate outcome. LET-60 therefore contributes to cell-fate specification, but this is a developmental target-cell response downstream of its Ras GTPase switch. Supporting Evidence: PMID:9486792 lin-39 is absolutely required for Ras signaling to induce vulval development |
| GO:0043274 phospholipase binding | IPI PMID:9497345 Identification of PLC210, a Caenorhabditis elegans phospholi... | ACCEPT | Summary: LET-60 binds the PLC-1/PLC210 Ras-associating domain, supporting this specific effector-binding annotation. Reason: The cited yeast two-hybrid screen searched for LET-60-binding proteins and identified PLC210/PLC-1 as a phospholipase C with a Ras-associating domain, directly supporting phospholipase binding as an effector interaction for LET-60. Supporting Evidence: PMID:9497345 we performed a yeast two-hybrid screening for LET-60-binding proteins |
| GO:0048477 oogenesis | IGI PMID:9472025 The Caenorhabditis elegans SH2 domain-containing protein tyr... | KEEP AS NON CORE | Summary: Activated LET-60 can rescue ptp-2 oogenesis defects, indicating a Ras/MAPK contribution to germ-line oogenesis. Reason: Genetic analysis placed LET-60 Ras downstream of or parallel to PTP-2 during oogenesis, and prior work connected LET-60/MEK-2/MPK-1 to the pachytene-to-diakinesis transition. Oogenesis is a real biological context for LET-60 signaling but is not the gene product's core molecular function. Supporting Evidence: PMID:9472025 Gain-of-function let-60 ras alleles rescued the defects associated with ptp-2(op194) |
| GO:0072327 vulval cell fate specification | IGI PMID:28135265 Ξ²-Integrin de-phosphorylation by the Density-Enhanced Phosph... | KEEP AS NON CORE | Summary: DEP-1/PAT-3 pathway genetics support LET-60 acting in vulval cell fate specification. Reason: The DEP-1 study probed regulators of LET-23 EGFR/Ras/MAPK signal strength in vulval precursor cells. Vulval cell fate specification is the canonical nematode output of the pathway and is kept here as a non-core developmental process. Supporting Evidence: PMID:28135265 DEP-1 mediates binary cell fate decisions by negatively regulating EGFR signaling |
| GO:0072327 vulval cell fate specification | IGI PMID:28135265 Ξ²-Integrin de-phosphorylation by the Density-Enhanced Phosph... | KEEP AS NON CORE | Summary: LET-60 contributes to LET-23/DEP-1-dependent vulval cell fate specification. Reason: DEP-1 and beta-integrin/talin tune the EGFR/Ras/MAPK pathway that drives primary versus secondary vulval precursor cell fates. The annotation is valid as a tissue-specific output of LET-60 signaling. Supporting Evidence: PMID:28135265 DEP-1 mediates binary cell fate decisions by negatively regulating EGFR signaling |
| GO:0072327 vulval cell fate specification | IGI PMID:28135265 Ξ²-Integrin de-phosphorylation by the Density-Enhanced Phosph... | KEEP AS NON CORE | Summary: The DEP-1/PAT-3 circuit modulates the LET-60-dependent vulval Ras/MAPK response. Reason: Genetic interactions in this study connect integrin, talin, DEP-1, LET-23, and LET-60 pathway activity in vulval precursor cells. The row should be retained as non-core because it describes a developmental consequence of LET-60 signaling. Supporting Evidence: PMID:28135265 DEP-1 mediates binary cell fate decisions by negatively regulating EGFR signaling |
| GO:0072327 vulval cell fate specification | IGI PMID:28135265 Ξ²-Integrin de-phosphorylation by the Density-Enhanced Phosph... | KEEP AS NON CORE | Summary: LET-60 is part of a DEP-1-regulated EGFR/Ras/MAPK module that specifies vulval precursor-cell fate. Reason: The cited IGI row is consistent with the local DEP-1/PAT-3 study: DEP-1 attenuates EGFR signaling at the LET-23 receptor and through beta-integrin effects on receptor mobility, thereby tuning the downstream LET-60/MAPK fate-specification response. This is non-core for LET-60. Supporting Evidence: PMID:28135265 DEP-1 attenuates EGFR signaling in part by de-phosphorylating Y792 |
| GO:0072327 vulval cell fate specification | IMP PMID:20230814 A strawberry notch homolog, let-765/nsh-1, positively regula... | KEEP AS NON CORE | Summary: LET-765/NSH-1 acts upstream of LIN-3/EGFR/Ras to promote LET-60-dependent vulval induction. Reason: The let-765 study places NSH-1 upstream of the LIN-3/LET-23/Ras pathway that patterns vulval precursor cells. The IMP row supports vulval cell fate specification as a downstream output of LET-60 signaling. Supporting Evidence: PMID:20230814 let-765/nsh-1, that functions upstream of the pathway to promote vulval induction |
| GO:0120283 protein serine/threonine kinase binding | IPI PMID:9674433 SUR-8, a conserved Ras-binding protein with leucine-rich rep... | ACCEPT | Summary: LET-60 binds LIN-45/Raf, a protein serine/threonine kinase effector. Reason: LIN-45/Raf is a serine/threonine kinase effector downstream of LET-60/Ras, and the Ras-binding domain of LIN-45 is necessary for full Raf function during C. elegans development. The specific kinase-binding term is informative and should be retained. Supporting Evidence: PMID:11861555 The lin-45 alleles include three missense mutations that affect the Ras-binding domain |
| GO:1902685 positive regulation of receptor localization to synapse | IMP PMID:25603799 A role for Ras in inhibiting circular foraging behavior as r... | KEEP AS NON CORE | Summary: LET-60 regulates GLR-1 receptor localization in RMD neurons during foraging behavior. Reason: Time- and cell-specific let-60 knockdown showed an adult neuronal Ras requirement for GLR-1 localization in RMD neurons. This is a valid specialized output of LET-60/Ras-MAPK signaling, not its conserved core activity. Supporting Evidence: PMID:25603799 GLR-1 localization in RMD neurons requires Ras at the adult stage |
Loading supporting contentβ¦
Download this section (compressed HTML)let-60 encodes a member of the GTP-binding RAS protooncogene family; let-60 activity is required for viability, vulval development, spicule development, germ line meiotic progression, posterior development of the hypodermis, chemotaxis, sex myoblast migration, and muscle membrane extension; let-60 acts genetically downstream of let-23 with respect to vulval development and upstream of the MAPK pathway with respect to chemotaxis; let-60 is expressed in neural, muscle, and hypodermal lineages.
Provider deep research was unavailable for this review because Falcon required
agentapi on PATH and the Perplexity/OpenAI fallbacks lacked API keys. This
pass therefore used the fetched UniProt record, GOA-seeded annotation review,
cached PMID records, and the local GO-CAM/Reactome context where present.
Loading supporting contentβ¦
Download this section (compressed HTML)