rsks-1 (Y47D3A.16) encodes RSKS-1, the sole Caenorhabditis elegans ortholog of the p70 ribosomal protein S6 kinase (S6K), a 550-residue AGC-family serine/threonine kinase with an N-terminal kinase domain, an AGC-kinase C-terminal domain carrying the TOR-site hydrophobic-motif threonine (T404) and a disordered C-terminal tail. RSKS-1 acts as a downstream effector of TORC1 (LET-363/TOR with DAF-15/RAPTOR), coupling nutrient and amino-acid signals to protein synthesis and growth. Loss of rsks-1 lowers protein synthesis, slows development, reduces brood size and extends adult lifespan and stress resistance through PHA-4/FoxA, HSF-1, AAK-2/AMPK and germline signalling. It acts germline-autonomously to expand the larval germline progenitor pool, promoting cell cycle progression and the proliferative fate, and cell-autonomously in touch neurons, where it is found in the perikaryon and axon, to restrain axon regeneration after injury via AAK-2. Adult knockdown reduces autophagy.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0002119 nematode larval development | IGI PMID:18804378 The Target of Rapamycin pathway antagonizes pha-4/FoxA to co... | KEEP AS NON CORE | Summary: rsks-1 mutations suppress the larval lethality of pha-4 loss, and rsks-1 RNAi (like raga-1/rheb-1 RNAi) blocks the nprl-3 rescue of elo-5 L1 arrest; RSKS-1 acts as a TORC1 output that promotes larval growth. Reason: Genetic-interaction evidence places RSKS-1 in the nutrient/TORC1 control of postembryonic development, but rsks-1 is not itself required to complete larval development (mutants are slow-growing but viable). The term is a broad developmental process downstream of the core signalling role, so it is kept as non-core. Supporting Evidence: PMID:18804378 rsks-1/S6 kinase mutations, but not ife-2/eIF4E, can suppress pha-4-associated larval lethality PMID:18804378 rsks-1/S6 kinase and ife-2/eIF4E each promoted protein biosynthesis, but neither was necessary to complete larval development or to localize FIB-1 PMID:23705068 We found that elo-5(−) nprl-3(ku540) animals treated with ife-2(RNAi) or rsks-1(RNAi), with or without C17ISO supplement, yielded results similar to those obtained with raga-1(RNAi) and rheb-1(RNAi) (Table 1) |
| GO:0004672 protein kinase activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro-based protein kinase activity. Correct but general; RSKS-1 is an AGC-family S6 kinase with a canonical Ser/Thr kinase domain. Reason: Correct but less specific than supported. Replace with protein serine/threonine kinase activity (GO:0004674), which the gene already carries by IBA and IEA. Proposed replacements: protein serine/threonine kinase activity Supporting Evidence: file:worm/rsks-1/rsks-1-uniprot.txt Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. S6 kinase subfamily. |
| GO:0004674 protein serine/threonine kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference of Ser/Thr kinase activity for the S6K/RSK node. RSKS-1 has an intact kinase domain (ATP-binding K115, catalytic D210) and the TOR-site T404 that is required for function in vivo. Reason: RSKS-1 is the C. elegans p70 S6 kinase ortholog, well inside the clade of experimentally characterized Ser/Thr S6 kinases (human S6K1 P23443 is among the seeds). The in vivo requirement for T404 and the loss of function of K115Q are consistent with a catalytically active kinase. Core molecular function. Supporting Evidence: file:worm/rsks-1/rsks-1-uniprot.txt Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. S6 kinase subfamily. PMID:22278922 the T404A transgene did not rescue the germline phenotype of rsks-1(sv31) file:worm/rsks-1/rsks-1-uniprot.txt K->Q: Probable loss of kinase activity. Enhanced axonal regrowth following axotomy of PLM neurons. |
| GO:0004674 protein serine/threonine kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Ser/Thr kinase activity from combined IEA methods (EC 2.7.11.1, AGC kinase InterPro signatures). Consistent with the IBA row. Reason: Same core claim as the IBA row, supported by family membership and conserved catalytic residues. Supporting Evidence: file:worm/rsks-1/rsks-1-uniprot.txt Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. S6 kinase subfamily. |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: ATP binding inferred from the protein kinase domain and ATP-binding site signatures. Reason: True for an active kinase (glycine-rich loop 89-97, K115) but subsumed in the catalytic activity; not informative on its own. Supporting Evidence: file:worm/rsks-1/rsks-1-uniprot.txt /ligand="ATP" |
| GO:0005654 nucleoplasm | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: PAINT nucleoplasm inference from the S6K/RSK node, seeded by mammalian S6Ks and RSKs. Reason: Mammalian S6K1 (p85 isoform) and RSKs have nuclear pools, so the node placement is reasonable, but there is no worm evidence of nuclear RSKS-1; the characterized worm localization is axon and perikaryon. Kept as plausible, non-core. Supporting Evidence: file:worm/rsks-1/rsks-1-uniprot.txt Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. S6 kinase subfamily. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT cytoplasm inference for the S6 kinase family. Consistent with the observed axonal and perikaryal (cytoplasmic) localization of RSKS-1 in neurons. Reason: S6 kinases act on cytoplasmic ribosomal and translational substrates; RSKS-1 localizes to the perikaryon and axon of touch neurons, both cytoplasmic compartments. Supporting Evidence: file:worm/rsks-1/rsks-1-uniprot.txt Cell projection, axon file:worm/rsks-1/rsks-1-uniprot.txt Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. S6 kinase subfamily. |
| GO:0007165 signal transduction | IEA GO_REF:0000002 | MODIFY | Summary: Signal transduction from the ribosomal S6 kinase InterPro signature. Correct but very general. Reason: RSKS-1 acts in TORC1 signaling (downstream of LET-363/TOR and DAF-15/RAPTOR); replace with GO:0038202 TORC1 signaling, which the gene already carries by IBA. Proposed replacements: TORC1 signaling Supporting Evidence: PMID:22278922 rsks-1 (S6K) acts downstream of let-363 (TOR) and daf -15 (RAPTOR) for proper larval expansion of the germline progenitor pool PMID:23705068 we used RNAi to knock down C. elegans orthologs of elf4E (ife-2) and p70S6K(rsks-1), two well-known downstream targets of TORC1 |
| GO:0008340 determination of adult lifespan | IGI PMID:20523893 Manipulation of behavioral decline in Caenorhabditis elegans... | KEEP AS NON CORE | Summary: rsks-1(ok1255) mutants live moderately longer than wild type, and raga-1 further extends their lifespan (genetic interaction with raga-1). Reason: Loss of rsks-1 reproducibly extends lifespan in several labs (also PMID:17266680, PMID:18804378, PMID:23879233). This is an organismal phenotype downstream of RSKS-1's role as a TORC1 effector kinase rather than its direct function, so it is kept as non-core. Supporting Evidence: PMID:20523893 rsks-1mutation produced a moderate increase in lifespan compared to wild-type (Figure S7) PMID:18804378 We observed a ~10% extension in lifespan for rsks-1(ok1255) in 4/4 experiments |
| GO:0008340 determination of adult lifespan | IMP PMID:17266679 Lifespan extension by conditions that inhibit translation in... | KEEP AS NON CORE | Summary: RNAi against rsks-1 extends lifespan (Hansen et al.). Reason: Loss of rsks-1 reproducibly extends lifespan in several labs (also PMID:17266680, PMID:18804378, PMID:23879233). This is an organismal phenotype downstream of RSKS-1's role as a TORC1 effector kinase rather than its direct function, so it is kept as non-core. Supporting Evidence: PMID:17266679 reducing the levels of ribosomal proteins, ribosomal-protein S6 kinase or translation-initiation factors increases the lifespan of Caenorhabditis elegans PMID:18804378 We observed a ~10% extension in lifespan for rsks-1(ok1255) in 4/4 experiments |
| GO:0008340 determination of adult lifespan | IMP NOT PMID:17277769 eIF4E function in somatic cells modulates ageing in Caenorha... | UNDECIDED | Summary: NOT annotation to determination of adult lifespan from the ife-2/eIF4E paper (Syntichaki et al. 2007). Only the abstract is available, which does not mention rsks-1. Reason: Cannot verify the experiment behind the NOT annotation (full text not accessible). It conflicts with multiple independent reports that rsks-1 loss extends lifespan, which may reflect a specific RNAi condition in this study. Deferring rather than removing an experimental curator call. Supporting Evidence: PMID:17266679 reducing the levels of ribosomal proteins, ribosomal-protein S6 kinase or translation-initiation factors increases the lifespan of Caenorhabditis elegans PMID:18804378 We observed a ~10% extension in lifespan for rsks-1(ok1255) in 4/4 experiments file:worm/rsks-1/rsks-1-deep-research-manual.md A NOT lifespan annotation from the ife-2 paper (PMID:17277769) could not be checked |
| GO:0008340 determination of adult lifespan | IMP PMID:20523893 Manipulation of behavioral decline in Caenorhabditis elegans... | KEEP AS NON CORE | Summary: rsks-1(ok1255) mutation produces a moderate lifespan increase. Reason: Loss of rsks-1 reproducibly extends lifespan in several labs (also PMID:17266680, PMID:18804378, PMID:23879233). This is an organismal phenotype downstream of RSKS-1's role as a TORC1 effector kinase rather than its direct function, so it is kept as non-core. Supporting Evidence: PMID:20523893 rsks-1mutation produced a moderate increase in lifespan compared to wild-type (Figure S7) PMID:18804378 We observed a ~10% extension in lifespan for rsks-1(ok1255) in 4/4 experiments |
| GO:0030424 axon | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Axon localization mapped from the UniProt subcellular location, which is experimentally based on PMID:24431434 (RSKS-1 enriched in the PLM synaptic branch). Reason: Experimentally grounded localization relevant to the neuronal (axon regeneration) role, which is peripheral to the core kinase/TORC1 function. Supporting Evidence: file:worm/rsks-1/rsks-1-uniprot.txt Cell projection, axon file:worm/rsks-1/rsks-1-uniprot.txt Enriched in the synaptic branch of PLM neurons. |
| GO:0038202 TORC1 signaling | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT TORC1 signaling inference for the S6K node. Worm genetics places RSKS-1 downstream of LET-363/TOR and DAF-15/RAPTOR, and RSKS-1 knockdown phenocopies loss of TORC1 activators in development. Reason: RSKS-1 is the canonical TORC1 substrate kinase; T404 (the TOR-site hydrophobic motif) is required for germline function, and epistasis with let-363/daf-15 and with raga-1/rheb-1 supports participation in TORC1 signaling. Supporting Evidence: PMID:22278922 rsks-1 (S6K) acts downstream of let-363 (TOR) and daf -15 (RAPTOR) for proper larval expansion of the germline progenitor pool PMID:22278922 the T404A transgene did not rescue the germline phenotype of rsks-1(sv31) PMID:23705068 we used RNAi to knock down C. elegans orthologs of elf4E (ife-2) and p70S6K(rsks-1), two well-known downstream targets of TORC1 |
| GO:0043204 perikaryon | EXP PMID:24431434 S6 kinase inhibits intrinsic axon regeneration capacity via ... | KEEP AS NON CORE | Summary: RSKS-1 reporter localized to the perikaryon of touch neurons (Hubert et al. 2014). Cached publication is abstract-only; localization recorded from the curated UniProt entry citing this paper. Reason: Experimental localization accepted from curators; peripheral to the core function. Supporting Evidence: file:worm/rsks-1/rsks-1-uniprot.txt Perikaryon PMID:24431434 we have identified the ribosomal S6 kinase RSKS-1 as a new cell-autonomous inhibitor of axon regeneration |
| GO:0043204 perikaryon | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Perikaryon mapped from UniProt subcellular location, which rests on PMID:24431434. Reason: Same experimentally grounded claim as the EXP row; non-core. Supporting Evidence: file:worm/rsks-1/rsks-1-uniprot.txt Perikaryon |
| GO:0106310 protein serine kinase activity | IEA GO_REF:0000116 | ACCEPT | Summary: Protein serine kinase activity from the Rhea reaction (RHEA:17989) in the UniProt entry (PIRNR rule). Reason: S6 kinases phosphorylate serine residues (e.g. ribosomal protein S6); consistent with the AGC S6K family membership. Accepted alongside GO:0004674. Supporting Evidence: file:worm/rsks-1/rsks-1-uniprot.txt Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. S6 kinase subfamily. |
| GO:2000786 positive regulation of autophagosome assembly | IMP PMID:22560223 TOR signaling and rapamycin influence longevity by regulatin... | KEEP AS NON CORE | Summary: Adult rsks-1 RNAi reduced GFP::LGG-1 autophagic puncta (Robida-Stubbs et al. 2012), supporting a positive role in autophagy. Reason: The full text supports the direction of the annotation. However it is a single RNAi readout, another study reports no autophagy change in rsks-1 mutants, and the mechanism is unknown; kept as non-core. The UniProt entry states the opposite direction and should be checked. Supporting Evidence: PMID:22560223 autophagy was reduced by knockdown of the S6 kinase RSKS-1, which increases translation downstream of TORC1 but also promotes autophagy |
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Download this section (compressed HTML)Q: Which proteins does RSKS-1 phosphorylate in vivo? Is ribosomal protein S6 (RPS-6) a direct substrate in C. elegans, and do distinct substrates mediate its lifespan, germline and axon-regeneration roles?
Q: Does RSKS-1 promote or inhibit autophagy? Robida-Stubbs et al. (PMID:22560223) report reduced LGG-1 puncta after rsks-1 RNAi, whereas the UniProt entry states the reverse and Sheaffer et al. report no change in mutants.
Q: What experiment underlies the NOT 'determination of adult lifespan' annotation from PMID:17277769, given the consistent lifespan extension reported elsewhere?
Experiment: In vitro kinase assay with immunopurified RSKS-1 (wild type, K115Q, T404A, T404E) on RPS-6 peptides, plus phospho-RPS-6 immunoblots in rsks-1 mutants and let-363/daf-15 RNAi worms.
Hypothesis: RSKS-1 is a TORC1-activated kinase that directly phosphorylates RPS-6, and T404 phosphorylation is required for its activity.
Experiment: Phosphoproteomics comparing wild type and rsks-1(ok1255) germline and neurons to identify tissue-specific RSKS-1 substrates.
Hypothesis: Distinct RSKS-1 substrates mediate germline proliferation, lifespan and axon regeneration phenotypes.
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