AGE-1 is the catalytic p110 subunit of the single class I phosphatidylinositol 3-kinase (PI3K) of Caenorhabditis elegans. It partners with the p50/p55-like adaptor subunit AAP-1 and, downstream of the insulin/IGF-1-like receptor DAF-2, phosphorylates phosphatidylinositol 4,5-bisphosphate to generate PIP3 at the inner leaflet of the plasma membrane. PIP3 recruits and activates PDK-1 and the AKT-1/AKT-2/SGK-1 kinases, which phosphorylate and exclude the FOXO transcription factor DAF-16 from the nucleus; the PTEN homolog DAF-18 opposes AGE-1 by removing the 3-phosphate. AGE-1 is found diffusely in the cytoplasm of most cells. Loss of maternal and zygotic age-1 causes constitutive dauer arrest, while partial loss greatly extends adult lifespan and increases stress resistance, effects that require daf-16. AGE-1 signalling also contributes to fertility, embryonic cell survival, and experience-dependent salt chemotaxis in sensory neurons.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005515 protein binding | IPI PMID:12393910 Insulin receptor substrate and p55 orthologous adaptor prote... | MODIFY | Summary: IPI with AAP-1 (G5EDP9), the sole C. elegans PI3K p50/p55 adaptor/regulatory subunit, from Wolkow et al. 2002. Reason: Generic protein binding is uninformative. The partner is the PI3K regulatory subunit AAP-1, and the same paper supports AGE-1 membership in the PI3K complex (IDA). The informative MF is binding of the catalytic subunit to its regulatory subunit (GO:0036312). The cached record is abstract-only, which names AAP-1 as the p50/p55 ortholog; the binding assay itself is in the full text the curator read. Proposed replacements: phosphatidylinositol 3-kinase regulatory subunit binding Supporting Evidence: PMID:12393910 The C. elegans versions of insulin receptor substrate (IST-1) and PI3K p50/p55 (AAP-1) share moderate sequence similarity with their vertebrate and Drosophila counterparts. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: IBA cytoplasm; class I PI3K catalytic subunits are cytosolic enzymes recruited to membranes on activation. Reason: Consistent with immunostaining showing diffuse cytoplasmic AGE-1 in wild-type worms (PMID:23543623). Supporting Evidence: PMID:23543623 registered full-length enzyme as a diffuse cytoplasmic signal in virtually all cell types of wild-type C. |
| GO:0005737 cytoplasm | IDA PMID:23543623 Extreme Depletion of PIP3 Accompanies the Increased Life Spa... | ACCEPT | Summary: IDA cytoplasm: an antibody to the AGE-1 helical/kinase domains gives a diffuse cytoplasmic signal in nearly all cells, absent in age-1(mg44) F2 homozygotes. Reason: Direct, specificity-controlled immunolocalisation. Supporting Evidence: PMID:23543623 registered full-length enzyme as a diffuse cytoplasmic signal in virtually all cell types of wild-type C. |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: IBA plasma membrane. Class I PI3K produces PIP3 on the inner leaflet of the plasma membrane, where PIP3 recruits PDK-1 and AKT kinases. Reason: The site of AGE-1 catalytic action is the plasma membrane inner leaflet; this is where its product acts (PMID:25383666). Phylogenetically sound. Supporting Evidence: PMID:25383666 In the IIS pathway, the insulin receptor-like protein DAF-2 activates the PI3K complex AGE-1/AAP-118β20, leading to the generation of PIP3 on the inner leaflet of the plasma membrane. |
| GO:0005942 phosphatidylinositol 3-kinase complex | IBA GO_REF:0000033 | ACCEPT | Summary: IBA PI3K complex. AGE-1 is the p110 catalytic subunit that partners with the AAP-1 p50/p55 regulatory subunit. Reason: Class IA PI3K is an obligate catalytic/regulatory heterodimer; AGE-1/AAP-1 is described as the worm PI3K complex. Supporting Evidence: PMID:25383666 In the IIS pathway, the insulin receptor-like protein DAF-2 activates the PI3K complex AGE-1/AAP-118β20, leading to the generation of PIP3 on the inner leaflet of the plasma membrane. |
| GO:0005942 phosphatidylinositol 3-kinase complex | IDA PMID:12393910 Insulin receptor substrate and p55 orthologous adaptor prote... | ACCEPT | Summary: IDA PI3K complex from Wolkow et al. 2002, who characterised AAP-1, the PI3K adaptor subunit that partners with AGE-1. Reason: Experimental support from the curator-read full text; consistent with the conserved class IA heterodimer architecture. Supporting Evidence: PMID:12393910 Genetic experiments show that ist-1 and aap-1 potentiate C. elegans insulin-like signaling, although they are not required for signaling in the pathway under most conditions. |
| GO:0005942 phosphatidylinositol 3-kinase complex | NAS PMID:8700226 A phosphatidylinositol-3-OH kinase family member regulating ... | ACCEPT | Summary: NAS PI3K complex from the age-1 cloning paper, which identified AGE-1 as a p110 catalytic subunit homolog. Reason: A p110 catalytic subunit by definition acts within the PI3K holoenzyme complex; consistent with the IBA and IDA rows. Supporting Evidence: PMID:8700226 age-1 encodes a homologue of mammalian phosphatidylinositol-3-OH kinase (PI(3)K) catalytic subunits. |
| GO:0006935 chemotaxis | IGI PMID:20837997 Reversal of salt preference is directed by the insulin/PI3K ... | KEEP AS NON CORE | Summary: IGI chemotaxis from salt-preference reversal (Adachi et al. 2010): PI3K signalling in ASER promotes learned salt avoidance. Reason: AGE-1 contributes to this behaviour as the PI3K step of DAF-2 signalling in specific sensory neurons; the behaviour is a downstream, cell-context-specific output of the signalling activity, not a separate function. Retained as a valid but non-core process. Supporting Evidence: PMID:20837997 This study shows that the PI 3-kinase signaling promotes aversive drive of ASER but not of ASEL. |
| GO:0006979 response to oxidative stress | IMP PMID:18828672 Caenorhabditis elegans HCF-1 functions in longevity maintena... | KEEP AS NON CORE | Summary: IMP response to oxidative stress (Li et al. 2008, HCF-1 paper), where age-1(hx546) served as the paraquat-resistant control strain. Reason: Reduced AGE-1 increases oxidative stress resistance via derepression of DAF-16. AGE-1 is thus a negative regulator of a stress-resistance programme rather than an executor of the response. Phenotype is real; keep as non-core. Supporting Evidence: PMID:18828672 The age-1(hx546) and daf-16(mgDf47) worms were included as controls as they have been previously reported to be either resistant or sensitive to paraquat, heavy metal, or heat shock, respectively [41β43]. |
| GO:0007611 learning or memory | IMP PMID:16950159 The insulin/PI 3-kinase pathway regulates salt chemotaxis le... | KEEP AS NON CORE | Summary: IMP learning or memory: age-1 mutants are defective in salt chemotaxis learning (Tomioka et al. 2006). Reason: AGE-1 contributes to this behaviour as the PI3K step of DAF-2 signalling in specific sensory neurons; the behaviour is a downstream, cell-context-specific output of the signalling activity, not a separate function. Retained as a valid but non-core process. Supporting Evidence: PMID:16950159 daf-2 and age-1 act in the ASER salt-sensing neuron, and the activity level of the DAF-2/AGE-1 pathway in this neuron determines the extent and orientation of salt chemotaxis. |
| GO:0007635 chemosensory behavior | IGI PMID:20837997 Reversal of salt preference is directed by the insulin/PI3K ... | KEEP AS NON CORE | Summary: IGI chemosensory behavior from Adachi et al. 2010 (salt chemotaxis plasticity). Reason: AGE-1 contributes to this behaviour as the PI3K step of DAF-2 signalling in specific sensory neurons; the behaviour is a downstream, cell-context-specific output of the signalling activity, not a separate function. Retained as a valid but non-core process. Supporting Evidence: PMID:20837997 This study shows that the PI 3-kinase signaling promotes aversive drive of ASER but not of ASEL. |
| GO:0008340 determination of adult lifespan | IGI PMID:17277769 eIF4E function in somatic cells modulates ageing in Caenorha... | ACCEPT | Summary: IGI lifespan (Syntichaki et al. 2007): ife-2 loss further extends the lifespan of long-lived age-1 mutants. Reason: AGE-1 activity shortens lifespan by repressing DAF-16; determination of adult lifespan is a hallmark, well-replicated role of age-1. Supporting Evidence: PMID:17277769 Furthermore, IFE-2 deficiency further extends the lifespan of long-lived age and daf nematode mutants. |
| GO:0008340 determination of adult lifespan | IGI PMID:19783783 Life-span extension by dietary restriction is mediated by NL... | ACCEPT | Summary: IGI lifespan (Park et al. 2010): nlp-7/cup-4 RNAi does not shorten reduced-IIS long-lived mutants such as age-1. Reason: Consistent with the extensive evidence that AGE-1 PI3K signalling sets adult lifespan. Supporting Evidence: PMID:19783783 has no effect on the life span of long-lived mutants resulting from reduced insulin/IGF-1 signaling or dysfunction of the mitochondrial electron transport chain |
| GO:0008340 determination of adult lifespan | IGI PMID:8601482 The age-1 and daf-2 genes function in a common pathway to co... | ACCEPT | Summary: IGI lifespan (Dorman et al. 1995): age-1 and daf-2 act in one lifespan pathway requiring daf-16 and daf-18. Reason: Foundational genetic evidence placing age-1 in the IIS lifespan pathway. Supporting Evidence: PMID:8601482 We found that the longevity of both age-1 and daf-2 mutants requires the activities of the same two genes, daf-16 and daf-18. |
| GO:0008340 determination of adult lifespan | IMP PMID:17277769 eIF4E function in somatic cells modulates ageing in Caenorha... | ACCEPT | Summary: IMP lifespan from Syntichaki et al. 2007 (age mutants are long-lived). Reason: age-1 loss-of-function extends lifespan; core organismal output of AGE-1 signalling. Supporting Evidence: PMID:17277769 Furthermore, IFE-2 deficiency further extends the lifespan of long-lived age and daf nematode mutants. |
| GO:0008340 determination of adult lifespan | IMP PMID:19783783 Life-span extension by dietary restriction is mediated by NL... | ACCEPT | Summary: IMP lifespan from Park et al. 2010. Reason: Consistent with the well-established long-lived phenotype of reduced-IIS mutants including age-1. Supporting Evidence: PMID:19783783 has no effect on the life span of long-lived mutants resulting from reduced insulin/IGF-1 signaling or dysfunction of the mitochondrial electron transport chain |
| GO:0008340 determination of adult lifespan | IMP PMID:9504918 An insulin-like signaling pathway affects both longevity and... | ACCEPT | Summary: IMP lifespan (Tissenbaum & Ruvkun 1998): maternally rescued age-1 alleles extend lifespan, suppressed by daf-16. Reason: Direct genetic evidence; AGE-1 is the PI3K step through which DAF-2 shortens lifespan. Supporting Evidence: PMID:9504918 These data show that insulin signaling, mediated by DAF-2 through the AGE-1 phosphatidylinositol-3-OH kinase, regulates reproduction and embryonic development, as well as dauer diapause and life span, and that DAF-16 transduces these signals. |
| GO:0008582 regulation of synaptic assembly at neuromuscular junction | IGI PMID:23665919 Attenuation of insulin signalling contributes to FSN-1-media... | KEEP AS NON CORE | Summary: IGI regulation of NMJ synaptic assembly (Hung et al. 2013): reducing insulin/IGF signalling in muscle partially rescues fsn-1 synapse defects. Reason: Genetic modifier evidence for a context-specific output of IIS in postsynaptic muscle. Valid but peripheral to AGE-1 core signalling function. Supporting Evidence: PMID:23665919 The aberrant synapse morphology and synaptic transmission in fsn-1 mutants are partially and specifically rescued by reducing insulin/IGF-signalling activity in postsynaptic muscles |
| GO:0009792 embryo development ending in birth or egg hatching | IMP PMID:9504918 An insulin-like signaling pathway affects both longevity and... | KEEP AS NON CORE | Summary: IMP embryo development: age-1 alleles reduce embryonic viability (Tissenbaum & Ruvkun 1998); AGE-1 also promotes embryonic cell survival via AKT (PMID:25383666). Reason: Real but pleiotropic developmental output of IIS; non-core. Supporting Evidence: PMID:9504918 These data show that insulin signaling, mediated by DAF-2 through the AGE-1 phosphatidylinositol-3-OH kinase, regulates reproduction and embryonic development, as well as dauer diapause and life span, and that DAF-16 transduces these signals. |
| GO:0016301 kinase activity | IEA GO_REF:0000002 | MODIFY | Summary: IEA kinase activity from InterPro PI3K/PI4K domain. Reason: Correct but very general; the physiologically relevant activity of a class I p110 is phosphorylation of PI(4,5)P2 to PIP3. Proposed replacements: 1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity Supporting Evidence: PMID:23543623 Such mutations insert a premature stop codon upstream of the catalytic domain of the AGE-1/p110Ξ± subunit of class-I PI3K. PMID:23543623 Class-I PI3Kβs convert PI(4,5)P2 (often abbreviated as PIP2) to PI(3,4,5)P3 (or PIP3), which plays decisive roles in multiple signaling pathways. |
| GO:0016303 1-phosphatidylinositol-3-kinase activity | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA 1-phosphatidylinositol-3-kinase activity (PI to PI3P), placed at a deep PI3K family node. Reason: All PI3K classes can phosphorylate PI in vitro, so this family-level activity is defensible for a class I enzyme, but the in vivo activity of AGE-1 is PIP2 to PIP3 (GO:0046934); PIP3 is undetectable in age-1 null F2 animals. Keep as non-core rather than argue with the PAINT node. Supporting Evidence: PMID:23543623 PIP3 is significantly reduced in first-generation age-1(mg44) homozygotes, and is below detectable limits in their second-generation progeny |
| GO:0016303 1-phosphatidylinositol-3-kinase activity | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: IEA (combined automated) 1-phosphatidylinositol-3-kinase activity. Reason: Same reasoning as the IBA row: plausible family-level in vitro activity, but not the physiological class I reaction (GO:0046934). Supporting Evidence: PMID:23543623 Class-I PI3Kβs convert PI(4,5)P2 (often abbreviated as PIP2) to PI(3,4,5)P3 (or PIP3), which plays decisive roles in multiple signaling pathways. |
| GO:0016303 1-phosphatidylinositol-3-kinase activity | ISS PMID:8700226 A phosphatidylinositol-3-OH kinase family member regulating ... | KEEP AS NON CORE | Summary: ISS 1-phosphatidylinositol-3-kinase activity from the age-1 cloning paper, based on homology to mammalian p110 catalytic subunits. Reason: The paper identifies AGE-1 as a homolog of mammalian class I p110 catalytic subunits; the characteristic physiological activity is PI(4,5)P2 3-kinase, proposed as NEW (GO:0046934). PI 3-kinase activity is a plausible in vitro family activity, kept as non-core for consistency with the IBA/IEA rows. Supporting Evidence: PMID:8700226 age-1 encodes a homologue of mammalian phosphatidylinositol-3-OH kinase (PI(3)K) catalytic subunits. PMID:23543623 PIP3 is significantly reduced in first-generation age-1(mg44) homozygotes, and is below detectable limits in their second-generation progeny |
| GO:0016303 1-phosphatidylinositol-3-kinase activity | NAS PMID:8700226 A phosphatidylinositol-3-OH kinase family member regulating ... | KEEP AS NON CORE | Summary: NAS 1-phosphatidylinositol-3-kinase activity from Morris et al. 1996. Reason: As for the ISS row: the p110 homology statement supports class I PIP2 3-kinase activity (NEW GO:0046934) as the core activity; this row is kept as non-core. Supporting Evidence: PMID:8700226 age-1 encodes a homologue of mammalian phosphatidylinositol-3-OH kinase (PI(3)K) catalytic subunits. |
| GO:0016477 cell migration | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA cell migration, propagated from PI3K family members with established roles in directed cell migration (e.g. mammalian and Dictyostelium class I PI3Ks). Reason: No C. elegans-specific evidence that AGE-1 drives cell migration, but also no evidence of loss; PI3K roles in migration are deeply conserved. Retain as non-core rather than overrule the PAINT node. Supporting Evidence: PMID:23543623 Class-I PI3Kβs convert PI(4,5)P2 (often abbreviated as PIP2) to PI(3,4,5)P3 (or PIP3), which plays decisive roles in multiple signaling pathways. |
| GO:0035005 1-phosphatidylinositol-4-phosphate 3-kinase activity | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA 1-phosphatidylinositol-4-phosphate 3-kinase activity (PI4P to PI(3,4)P2). Reason: Class I PI3Ks can phosphorylate PI4P in vitro, and the class IA complex term definition itself mentions this activity, but the physiological AGE-1 reaction is PIP2 to PIP3 (GO:0046934). Non-core. Supporting Evidence: PMID:23543623 Class-I PI3Kβs convert PI(4,5)P2 (often abbreviated as PIP2) to PI(3,4,5)P3 (or PIP3), which plays decisive roles in multiple signaling pathways. |
| GO:0036092 phosphatidylinositol-3-phosphate biosynthetic process | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: IBA phosphatidylinositol-3-phosphate biosynthetic process. Reason: Bulk PI3P synthesis is the role of class III PI3K (VPS34; vps-34 in C. elegans), not of class I p110 enzymes. AGE-1 has class I (p110) homology and its in vivo product is PIP3. Likely propagated from a deep node that includes class III activities. Propagation Review Root cause: PROPAGATION BAD Failure modes: FUNCTIONAL DIVERGENCE Sources checked: PANTHER:PTN000005674 Β· PTN000005674 SUPPORTS SOURCE BUT NOT TARGET Deep PI3K node whose PI3P-synthesis assertion reflects class III (VPS34-type) members; AGE-1 belongs to the class I p110 lineage whose in vivo product is PIP3. Supporting Evidence: PMID:23543623 Such mutations insert a premature stop codon upstream of the catalytic domain of the AGE-1/p110Ξ± subunit of class-I PI3K. PMID:23543623 Class-I PI3Kβs convert PI(4,5)P2 (often abbreviated as PIP2) to PI(3,4,5)P3 (or PIP3), which plays decisive roles in multiple signaling pathways. |
| GO:0040024 dauer larval development | IMP PMID:8700226 A phosphatidylinositol-3-OH kinase family member regulating ... | ACCEPT | Summary: IMP dauer larval development: loss of maternal and zygotic age-1 causes constitutive dauer formation. Reason: Hallmark phenotype; AGE-1 signalling prevents dauer arrest under favourable conditions. Supporting Evidence: PMID:8700226 Lack of both maternal and zygotic age-1 activity causes dauer formation, whereas animals with maternal but not zygotic age-1 activity develop as non-dauers that live more than twice as long as normal. |
| GO:0043053 dauer entry | IMP PMID:9504918 An insulin-like signaling pathway affects both longevity and... | ACCEPT | Summary: IMP dauer entry from Tissenbaum & Ruvkun 1998. Reason: age-1 mutants arrest at dauer; AGE-1 acts in the DAF-2 pathway that controls the dauer decision. Supporting Evidence: PMID:9504918 These data show that insulin signaling, mediated by DAF-2 through the AGE-1 phosphatidylinositol-3-OH kinase, regulates reproduction and embryonic development, as well as dauer diapause and life span, and that DAF-16 transduces these signals. |
| GO:0043491 phosphatidylinositol 3-kinase/protein kinase B signal transduction | IBA GO_REF:0000033 | ACCEPT | Summary: IBA PI3K/PKB signal transduction. Reason: AGE-1 is the PI3K that initiates this cassette in C. elegans: its PIP3 product recruits PDK-1 and AKT-1/2; core process. Supporting Evidence: PMID:25383666 In the IIS pathway, the insulin receptor-like protein DAF-2 activates the PI3K complex AGE-1/AAP-118β20, leading to the generation of PIP3 on the inner leaflet of the plasma membrane. PMID:25383666 elegans AKT kinases are likely activated by PIP3 and thus regulated by AGE-1, a PI3K that phosphorylates PIP2 to generate PIP319,20. |
| GO:0046686 response to cadmium ion | IMP PMID:18828672 Caenorhabditis elegans HCF-1 functions in longevity maintena... | KEEP AS NON CORE | Summary: IMP response to cadmium ion (HCF-1 paper; age-1(hx546) used as a heavy-metal-resistant control). Reason: Indirect: reduced AGE-1 derepresses DAF-16-dependent stress resistance. Non-core. Supporting Evidence: PMID:18828672 The age-1(hx546) and daf-16(mgDf47) worms were included as controls as they have been previously reported to be either resistant or sensitive to paraquat, heavy metal, or heat shock, respectively [41β43]. |
| GO:0046854 phosphatidylinositol phosphate biosynthetic process | IEA GO_REF:0000002 | ACCEPT | Summary: IEA phosphatidylinositol phosphate biosynthetic process. Reason: AGE-1 synthesises PIP3; PIP3 is undetectable in age-1 null F2 animals. Appropriately general. Supporting Evidence: PMID:23543623 PIP3 is significantly reduced in first-generation age-1(mg44) homozygotes, and is below detectable limits in their second-generation progeny |
| GO:0048015 phosphatidylinositol-mediated signaling | IBA GO_REF:0000033 | ACCEPT | Summary: IBA phosphatidylinositol-mediated signaling. Reason: AGE-1-generated PIP3 is the second messenger of DAF-2 signalling. Supporting Evidence: PMID:8700226 age-1 encodes a homologue of mammalian phosphatidylinositol-3-OH kinase (PI(3)K) catalytic subunits. PMID:8700226 These data suggest that phosphatidylinositol signalling mediated by AGE-1 protein controls lifespan and the dauer diapause decision. |
| GO:0050920 regulation of chemotaxis | IMP PMID:16950159 The insulin/PI 3-kinase pathway regulates salt chemotaxis le... | KEEP AS NON CORE | Summary: IMP regulation of chemotaxis (salt chemotaxis learning in ASER). Reason: AGE-1 contributes to this behaviour as the PI3K step of DAF-2 signalling in specific sensory neurons; the behaviour is a downstream, cell-context-specific output of the signalling activity, not a separate function. Retained as a valid but non-core process. Supporting Evidence: PMID:16950159 daf-2 and age-1 act in the ASER salt-sensing neuron, and the activity level of the DAF-2/AGE-1 pathway in this neuron determines the extent and orientation of salt chemotaxis. |
| GO:0097730 non-motile cilium | IDA PMID:16968739 IFTA-2 is a conserved cilia protein involved in pathways reg... | KEEP AS NON CORE | Summary: IDA non-motile cilium from the IFTA-2 paper (Schafer et al. 2006), which places DAF-2 pathway signalling in ciliated sensory neurons. Reason: The cached record is abstract-only and does not describe the AGE-1 localisation experiment; deferring to the curator who read the full text. A ciliary pool would be a sensory-neuron-specific site, not the general site of AGE-1 action (cytoplasm/plasma membrane), so non-core. Supporting Evidence: PMID:16968739 Our analysis indicates that these phenotypes result from defects in the DAF-2 (insulin-IGF-1-like) receptor signaling pathway in ciliated sensory neurons. |
| GO:0160108 animal gross anatomical part developmental process | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: ARBA IEA animal gross anatomical part developmental process. Reason: Vague machine-learned term with no specific supporting evidence for AGE-1 in gross anatomical development; developmental roles of AGE-1 are better captured by dauer and embryo development terms. Supporting Evidence: PMID:9504918 These data show that insulin signaling, mediated by DAF-2 through the AGE-1 phosphatidylinositol-3-OH kinase, regulates reproduction and embryonic development, as well as dauer diapause and life span, and that DAF-16 transduces these signals. |
| GO:1902074 response to salt | IGI PMID:20837997 Reversal of salt preference is directed by the insulin/PI3K ... | KEEP AS NON CORE | Summary: IGI response to salt (salt chemotaxis plasticity, Adachi et al. 2010). Reason: AGE-1 contributes to this behaviour as the PI3K step of DAF-2 signalling in specific sensory neurons; the behaviour is a downstream, cell-context-specific output of the signalling activity, not a separate function. Retained as a valid but non-core process. Supporting Evidence: PMID:20837997 This study shows that the PI 3-kinase signaling promotes aversive drive of ASER but not of ASEL. |
| GO:1902075 cellular response to salt | IGI PMID:24013594 Neuropeptide signaling remodels chemosensory circuit composi... | KEEP AS NON CORE | Summary: IGI cellular response to salt (Leinwand & Chalasani 2013): DAF-2/AGE-1 act in AWCON to respond to large salt changes. Reason: AGE-1 contributes to this behaviour as the PI3K step of DAF-2 signalling in specific sensory neurons; the behaviour is a downstream, cell-context-specific output of the signalling activity, not a separate function. Retained as a valid but non-core process. Supporting Evidence: PMID:24013594 AWCON NaCl responses are much reduced in age-1 mutants and normal responses are restored to animals when AGE-1 function is specifically rescued in AWCON (Fig. |
| GO:1902075 cellular response to salt | IGI PMID:24013594 Neuropeptide signaling remodels chemosensory circuit composi... | KEEP AS NON CORE | Summary: IGI cellular response to salt (second genetic interaction row, same paper). Reason: AGE-1 contributes to this behaviour as the PI3K step of DAF-2 signalling in specific sensory neurons; the behaviour is a downstream, cell-context-specific output of the signalling activity, not a separate function. Retained as a valid but non-core process. Supporting Evidence: PMID:24013594 AWCON NaCl responses are much reduced in age-1 mutants and normal responses are restored to animals when AGE-1 function is specifically rescued in AWCON (Fig. |
| GO:1902075 cellular response to salt | IMP PMID:24013594 Neuropeptide signaling remodels chemosensory circuit composi... | KEEP AS NON CORE | Summary: IMP cellular response to salt: age-1 mutants have reduced AWCON salt responses, rescued by AWCON-specific AGE-1. Reason: AGE-1 contributes to this behaviour as the PI3K step of DAF-2 signalling in specific sensory neurons; the behaviour is a downstream, cell-context-specific output of the signalling activity, not a separate function. Retained as a valid but non-core process. Supporting Evidence: PMID:24013594 AWCON NaCl responses are much reduced in age-1 mutants and normal responses are restored to animals when AGE-1 function is specifically rescued in AWCON (Fig. |
| GO:0046934 1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity | IMP PMID:23543623 Extreme Depletion of PIP3 Accompanies the Increased Life Spa... | NEW | Summary: AGE-1 is the sole class I (p110) PI3K catalytic subunit in C. elegans; PIP3 falls below detection in second-generation age-1(mg44) nulls. Reason: This is the core catalytic activity of AGE-1 and is the activity the DAF-2 module assigns to it, but GOA carries only the less specific PI to PI3P and PI4P 3-kinase terms. AGE-1 itself performs the catalytic step. Supported by p110 homology (PMID:8700226) and by loss of PIP3 in age-1 nulls. Supporting Evidence: PMID:23543623 PIP3 is significantly reduced in first-generation age-1(mg44) homozygotes, and is below detectable limits in their second-generation progeny PMID:23543623 Such mutations insert a premature stop codon upstream of the catalytic domain of the AGE-1/p110Ξ± subunit of class-I PI3K. PMID:23543623 Class-I PI3Kβs convert PI(4,5)P2 (often abbreviated as PIP2) to PI(3,4,5)P3 (or PIP3), which plays decisive roles in multiple signaling pathways. |
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Download this section (compressed HTML)Q: Does AGE-1 bind AAP-1 constitutively in all tissues, and does AGE-1 retain partial activity without AAP-1 (aap-1 mutants have weak phenotypes)?
Q: Is there a functionally relevant ciliary pool of AGE-1 in amphid sensory neurons?
Experiment: In vitro lipid kinase assays of recombinant AGE-1/AAP-1 with PI, PI4P and PI(4,5)P2 substrates to establish substrate preference directly for the nematode enzyme.
Hypothesis: AGE-1 prefers PI(4,5)P2 like mammalian class IA p110 enzymes.
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