pptr-1 encodes a B56 (B prime) regulatory subunit of the heterotrimeric serine/threonine protein phosphatase PP2A in Caenorhabditis elegans. The protein has an ARM-like helical B56 domain. With the scaffold PAA-1 and the catalytic subunit LET-92, it targets PP2A to specific phosphoproteins in the cytoplasm. In insulin/IGF-1 signaling, PPTR-1 binds AKT-1 and promotes dephosphorylation of its activation-loop Thr350. This lowers AKT-1 activity, allows DAF-16/FOXO nuclear entry, and affects dauer formation, lifespan, fat storage and stress resistance; mammalian B56beta acts the same way on Akt Thr308. In the early embryo, maternal PPTR-1, redundantly with PPTR-2, dephosphorylates the intrinsically disordered MEG proteins (MEG-1, MEG-3) that are phosphorylated by MBK-2/DYRK. This promotes condensation and stability of P granules so that they segregate to the germline. pptr-1 mutants partition P granule components equally to somatic and germline blastomeres but remain fertile except at high temperature.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000159 protein phosphatase type 2A complex | IBA GO_REF:0000033 | ACCEPT | Summary: B56-family member of the PP2A holoenzyme. Reason: PPTR-1 is a B56 (B prime) regulatory subunit of PP2A. RNAi of the catalytic (let-92), scaffold (paa-1) and pptr-1 subunits gives the same phenotypes (PMID:33315870), and PPTR-1 acts with PAA-1/LET-92 on P granules (PMID:25535836). The IBA is well placed in the B56 family. Supporting Evidence: PMID:19249087 An RNAi screen for serine/threonine protein phosphatases that counterbalance the effect of the kinases in the IIS pathway identified pptr-1, a B56 regulatory subunit of the PP2A holoenzyme. PMID:33315870 we found that three genes encoding the subunits to constitute a complete PP2A complex consisting of the catalytic subunit LET-92 along with the regulatory subunit PPTR-1 and the scaffold PAA-1 were required for Day 6 adults to resist ultraviolet irradiation |
| GO:0000159 protein phosphatase type 2A complex | IC PMID:19249087 A PP2A regulatory subunit regulates C. elegans insulin/IGF-1... | ACCEPT | Summary: Curator inference that PPTR-1, a B56 subunit, is part of PP2A. Reason: PPTR-1 is a B56 (B prime) regulatory subunit of PP2A. RNAi of the catalytic (let-92), scaffold (paa-1) and pptr-1 subunits gives the same phenotypes (PMID:33315870), and PPTR-1 acts with PAA-1/LET-92 on P granules (PMID:25535836). Supporting Evidence: PMID:19249087 An RNAi screen for serine/threonine protein phosphatases that counterbalance the effect of the kinases in the IIS pathway identified pptr-1, a B56 regulatory subunit of the PP2A holoenzyme. |
| GO:0000159 protein phosphatase type 2A complex | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro PP2A_B56 mapping to the PP2A complex. Reason: IPR002554 is diagnostic of B56 regulatory subunits, and the mapping agrees with the IBA and experimental context. Supporting Evidence: PMID:19249087 An RNAi screen for serine/threonine protein phosphatases that counterbalance the effect of the kinases in the IIS pathway identified pptr-1, a B56 regulatory subunit of the PP2A holoenzyme. |
| GO:0000159 protein phosphatase type 2A complex | NAS PMID:23336080 Suppressor mutations identify amino acids in PAA-1/PR65 that... | ACCEPT | Summary: Statement in an RSA-1/PAA-1 paper describing PPTR-1 as a PP2A regulatory subunit. Reason: The paper refers to PPTR-1 as a PP2A regulatory subunit in passing. It is consistent with all other evidence. Supporting Evidence: PMID:23336080 while a mutation in the regulatory subunit PPTR-1/B′ affects P-granule partitioning |
| GO:0005515 protein binding | IPI PMID:19249087 A PP2A regulatory subunit regulates C. elegans insulin/IGF-1... | REMOVE | Summary: Co-immunoprecipitation of PPTR-1 with AKT-1 from worm lysates. Reason: The PPTR-1/AKT-1 interaction is real and important: PPTR-1 targets PP2A to AKT-1 to dephosphorylate Thr350. Generic protein binding adds no information, and the same interaction is already captured by the protein kinase binding row and the phosphatase activator activity rows. Removal does not dispute the interaction. Supporting Evidence: PMID:19249087 In this study, we show that PPTR-1 directly interacts with AKT-1 and regulates its activity by modulating its phosphorylation, predominantly at the Thr 350 site. |
| GO:0005515 protein binding | IPI PMID:25535836 Regulation of RNA granule dynamics by phosphorylation of ser... | REMOVE | Summary: Yeast two-hybrid and GST pull-down binding of PPTR-1 to the P granule protein MEG-1. Reason: MEG-1 is a PP2A(PPTR-1) substrate in P granule assembly (PMID:25535836). The binding reflects B56-mediated substrate recruitment, which the phosphatase activator/regulator activity and P granule assembly rows already capture. Generic protein binding is uninformative; removal does not dispute the interaction. Supporting Evidence: PMID:25535836 Phosphorylation of the MEGs promotes granule disassembly and dephosphorylation promotes granule assembly. |
| GO:0005515 protein binding | IPI PMID:25535836 Regulation of RNA granule dynamics by phosphorylation of ser... | REMOVE | Summary: Yeast two-hybrid and GST pull-down binding of PPTR-1 to the P granule protein MEG-3. Reason: MEG-3 is a PP2A(PPTR-1) substrate in P granule assembly (PMID:25535836). The binding reflects B56-mediated substrate recruitment, which the phosphatase activator/regulator activity and P granule assembly rows already capture. Generic protein binding is uninformative; removal does not dispute the interaction. Supporting Evidence: PMID:25535836 Phosphorylation of the MEGs promotes granule disassembly and dephosphorylation promotes granule assembly. |
| GO:0005515 protein binding | IPI PMID:25535836 Regulation of RNA granule dynamics by phosphorylation of ser... | REMOVE | Summary: Yeast two-hybrid and GST pull-down binding of PPTR-1 to the P granule protein MEG-4. Reason: MEG-4 is a PP2A(PPTR-1) substrate in P granule assembly (PMID:25535836). The binding reflects B56-mediated substrate recruitment, which the phosphatase activator/regulator activity and P granule assembly rows already capture. Generic protein binding is uninformative; removal does not dispute the interaction. Supporting Evidence: PMID:25535836 Phosphorylation of the MEGs promotes granule disassembly and dephosphorylation promotes granule assembly. |
| GO:0005634 nucleus | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Nuclear localization inferred from B56-family members. Reason: Several mammalian B56 isoforms act in the nucleus, but tagged PPTR-1 in worms is predominantly cytosolic with little DAPI overlap (PMID:19249087). A minor nuclear pool cannot be excluded, so the IBA is kept as non-core rather than removed. Supporting Evidence: PMID:19249087 We find that PPTR-1 is predominantly cytosolic with little DAPI overlap |
| GO:0005737 cytoplasm | EXP PMID:19249087 A PP2A regulatory subunit regulates C. elegans insulin/IGF-1... | ACCEPT | Summary: Tagged PPTR-1 is cytoplasmic. Reason: PPTR-1::mCherry is predominantly cytosolic in worms. Supporting Evidence: PMID:19249087 We find that PPTR-1 is predominantly cytosolic with little DAPI overlap |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular location mapping (cytoplasm). Reason: Consistent with the experimental localization. Supporting Evidence: PMID:19249087 We find that PPTR-1 is predominantly cytosolic with little DAPI overlap |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: Cytosolic localization inferred for the B56 family. Reason: Consistent with experimental localization of PPTR-1 (PMID:19249087). PPTR-1 also enriches on embryonic P granules, which lie in the cytoplasm. Supporting Evidence: PMID:19249087 We find that PPTR-1 is predominantly cytosolic with little DAPI overlap |
| GO:0005829 cytosol | IDA PMID:19249087 A PP2A regulatory subunit regulates C. elegans insulin/IGF-1... | ACCEPT | Summary: PPTR-1::mCherry is predominantly cytosolic. Reason: Direct imaging shows PPTR-1 is predominantly cytosolic. Supporting Evidence: PMID:19249087 We find that PPTR-1 is predominantly cytosolic with little DAPI overlap |
| GO:0007165 signal transduction | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro PP2A_B56 mapping to signal transduction. Reason: Very broad. PPTR-1 regulates insulin/IGF-1 signaling by dephosphorylating AKT-1, which is captured more precisely by negative regulation of insulin receptor signaling pathway. Kept as non-core. Supporting Evidence: PMID:19249087 In this study, we show that PPTR-1 directly interacts with AKT-1 and regulates its activity by modulating its phosphorylation, predominantly at the Thr 350 site. |
| GO:0008340 determination of adult lifespan | IGI PMID:19249087 A PP2A regulatory subunit regulates C. elegans insulin/IGF-1... | KEEP AS NON CORE | Summary: pptr-1 modulates lifespan through the daf-2/daf-16 insulin pathway. Reason: pptr-1 RNAi suppresses daf-2 lifespan phenotypes in a daf-16-dependent way (PMID:19249087). This is a downstream organismal readout of the PPTR-1 effect on AKT-1 phosphorylation and DAF-16 localization, not a separate function. Kept as non-core. Supporting Evidence: PMID:19249087 Modulation of pptr-1 affects IIS pathway-associated phenotypes including life span, dauer, stress resistance, and fat storage. PMID:19249087 Taken together, our data suggests that PPTR-1 positively regulates DAF-16 nuclear localization and thereby its activity. |
| GO:0009408 response to heat | IGI PMID:19249087 A PP2A regulatory subunit regulates C. elegans insulin/IGF-1... | KEEP AS NON CORE | Summary: pptr-1 modulates heat stress resistance through the daf-2/daf-16 insulin pathway. Reason: pptr-1 RNAi suppresses daf-2 heat stress resistance phenotypes in a daf-16-dependent way (PMID:19249087). This is a downstream organismal readout of the PPTR-1 effect on AKT-1 phosphorylation and DAF-16 localization, not a separate function. Kept as non-core. Supporting Evidence: PMID:19249087 Modulation of pptr-1 affects IIS pathway-associated phenotypes including life span, dauer, stress resistance, and fat storage. PMID:19249087 Taken together, our data suggests that PPTR-1 positively regulates DAF-16 nuclear localization and thereby its activity. |
| GO:0010883 regulation of lipid storage | IGI PMID:19249087 A PP2A regulatory subunit regulates C. elegans insulin/IGF-1... | KEEP AS NON CORE | Summary: pptr-1 modulates fat storage through the daf-2/daf-16 insulin pathway. Reason: pptr-1 RNAi suppresses daf-2 fat storage phenotypes in a daf-16-dependent way (PMID:19249087). This is a downstream organismal readout of the PPTR-1 effect on AKT-1 phosphorylation and DAF-16 localization, not a separate function. Kept as non-core. Supporting Evidence: PMID:19249087 Modulation of pptr-1 affects IIS pathway-associated phenotypes including life span, dauer, stress resistance, and fat storage. PMID:19249087 Taken together, our data suggests that PPTR-1 positively regulates DAF-16 nuclear localization and thereby its activity. |
| GO:0019888 protein phosphatase regulator activity | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro PP2A_B56 mapping to protein phosphatase regulator activity. Reason: Correct parent of the more specific activator activity rows. Supporting Evidence: PMID:19249087 We show that PPTR-1 functions by regulating worm AKT-1 phosphorylation at Thr 350. |
| GO:0019901 protein kinase binding | IPI PMID:19249087 A PP2A regulatory subunit regulates C. elegans insulin/IGF-1... | KEEP AS NON CORE | Summary: PPTR-1 co-immunoprecipitates with the kinase AKT-1. Reason: AKT-1 is the kinase substrate that PPTR-1 recruits PP2A to. The binding is part of the regulatory-subunit function rather than a separate activity, so it is kept as non-core. Supporting Evidence: PMID:19249087 In this study, we show that PPTR-1 directly interacts with AKT-1 and regulates its activity by modulating its phosphorylation, predominantly at the Thr 350 site. |
| GO:0040024 dauer larval development | IGI PMID:19249087 A PP2A regulatory subunit regulates C. elegans insulin/IGF-1... | KEEP AS NON CORE | Summary: pptr-1 modulates dauer formation through the daf-2/daf-16 insulin pathway. Reason: pptr-1 RNAi suppresses daf-2 dauer formation phenotypes in a daf-16-dependent way (PMID:19249087). This is a downstream organismal readout of the PPTR-1 effect on AKT-1 phosphorylation and DAF-16 localization, not a separate function. Kept as non-core. Supporting Evidence: PMID:19249087 Modulation of pptr-1 affects IIS pathway-associated phenotypes including life span, dauer, stress resistance, and fat storage. PMID:19249087 Taken together, our data suggests that PPTR-1 positively regulates DAF-16 nuclear localization and thereby its activity. |
| GO:0046627 negative regulation of insulin receptor signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: PPTR-1/PP2A dephosphorylates AKT-1 Thr350, dampening insulin/IGF-1 signaling and promoting DAF-16 nuclear entry. Reason: PPTR-1 overexpression lowers phospho-AKT-1 and pptr-1 loss raises it; the effect on DAF-16 and on daf-2 phenotypes depends on akt-1 and daf-16. The conserved mammalian B56beta regulates Akt Thr308 the same way (PMID:19249087). This is a core process for PPTR-1. Supporting Evidence: PMID:19249087 We show that PPTR-1 functions by regulating worm AKT-1 phosphorylation at Thr 350. PMID:19249087 Taken together, our data suggests that PPTR-1 positively regulates DAF-16 nuclear localization and thereby its activity. |
| GO:0046627 negative regulation of insulin receptor signaling pathway | IGI PMID:19249087 A PP2A regulatory subunit regulates C. elegans insulin/IGF-1... | ACCEPT | Summary: PPTR-1/PP2A dephosphorylates AKT-1 Thr350, dampening insulin/IGF-1 signaling and promoting DAF-16 nuclear entry. Reason: PPTR-1 overexpression lowers phospho-AKT-1 and pptr-1 loss raises it; the effect on DAF-16 and on daf-2 phenotypes depends on akt-1 and daf-16. The conserved mammalian B56beta regulates Akt Thr308 the same way (PMID:19249087). This is a core process for PPTR-1. Supporting Evidence: PMID:19249087 We show that PPTR-1 functions by regulating worm AKT-1 phosphorylation at Thr 350. PMID:19249087 Taken together, our data suggests that PPTR-1 positively regulates DAF-16 nuclear localization and thereby its activity. |
| GO:0046627 negative regulation of insulin receptor signaling pathway | NAS PMID:19249087 A PP2A regulatory subunit regulates C. elegans insulin/IGF-1... | ACCEPT | Summary: PPTR-1/PP2A dephosphorylates AKT-1 Thr350, dampening insulin/IGF-1 signaling and promoting DAF-16 nuclear entry. Reason: PPTR-1 overexpression lowers phospho-AKT-1 and pptr-1 loss raises it; the effect on DAF-16 and on daf-2 phenotypes depends on akt-1 and daf-16. The conserved mammalian B56beta regulates Akt Thr308 the same way (PMID:19249087). This is a core process for PPTR-1. Supporting Evidence: PMID:19249087 We show that PPTR-1 functions by regulating worm AKT-1 phosphorylation at Thr 350. PMID:19249087 Taken together, our data suggests that PPTR-1 positively regulates DAF-16 nuclear localization and thereby its activity. |
| GO:0072542 protein phosphatase activator activity | IBA GO_REF:0000033 | ACCEPT | Summary: B56 regulatory subunits activate and target PP2A catalytic activity. Reason: B56 subunits direct the PP2A core enzyme to specific substrates. For PPTR-1 these are AKT-1 (PMID:19249087) and MEG-1/MEG-3 (PMID:25535836). The IBA node includes pptr-1 itself as an experimental source, which is expected. Supporting Evidence: PMID:19249087 We show that PPTR-1 functions by regulating worm AKT-1 phosphorylation at Thr 350. PMID:25535836 Phosphorylation of the MEGs promotes granule disassembly and dephosphorylation promotes granule assembly. |
| GO:0072542 protein phosphatase activator activity | IDA PMID:19249087 A PP2A regulatory subunit regulates C. elegans insulin/IGF-1... | ACCEPT | Summary: PPTR-1 levels control AKT-1 Thr350 dephosphorylation. Reason: The evidence is in vivo: PPTR-1 overexpression reduces and depletion increases AKT-1 phosphorylation. It shows that PPTR-1 promotes PP2A activity toward AKT-1, which matches the conventional B56 activity term. Supporting Evidence: PMID:19249087 We show that PPTR-1 functions by regulating worm AKT-1 phosphorylation at Thr 350. |
| GO:1903863 P granule assembly | IGI PMID:25535836 Regulation of RNA granule dynamics by phosphorylation of ser... | ACCEPT | Summary: PP2A(PPTR-1) dephosphorylates MEG proteins to promote P granule assembly and stability in the zygote. Reason: In pptr-1 mutants zygote P granules fail to grow and disassemble at each division (PMID:21127218, PMID:25535836). PPTR-1 acts redundantly with PPTR-2 and opposes the kinase MBK-2; meg-3/meg-4 loss is epistatic. PPTR-1 does part of the work as the regulatory subunit that targets PP2A to the MEG substrates, so the process annotation is a core one. Supporting Evidence: PMID:25535836 Phosphorylation of the MEGs promotes granule disassembly and dephosphorylation promotes granule assembly. PMID:21127218 We have identified a mutant (pptr-1) in which P granules become unstable during mitosis and P granule proteins and RNAs are distributed equally to somatic and germline blastomeres. |
| GO:1903863 P granule assembly | IGI PMID:25535836 Regulation of RNA granule dynamics by phosphorylation of ser... | ACCEPT | Summary: PP2A(PPTR-1) dephosphorylates MEG proteins to promote P granule assembly and stability in the zygote. Reason: In pptr-1 mutants zygote P granules fail to grow and disassemble at each division (PMID:21127218, PMID:25535836). PPTR-1 acts redundantly with PPTR-2 and opposes the kinase MBK-2; meg-3/meg-4 loss is epistatic. PPTR-1 does part of the work as the regulatory subunit that targets PP2A to the MEG substrates, so the process annotation is a core one. Supporting Evidence: PMID:25535836 Phosphorylation of the MEGs promotes granule disassembly and dephosphorylation promotes granule assembly. PMID:21127218 We have identified a mutant (pptr-1) in which P granules become unstable during mitosis and P granule proteins and RNAs are distributed equally to somatic and germline blastomeres. |
| GO:1903863 P granule assembly | IGI PMID:25535836 Regulation of RNA granule dynamics by phosphorylation of ser... | ACCEPT | Summary: PP2A(PPTR-1) dephosphorylates MEG proteins to promote P granule assembly and stability in the zygote. Reason: In pptr-1 mutants zygote P granules fail to grow and disassemble at each division (PMID:21127218, PMID:25535836). PPTR-1 acts redundantly with PPTR-2 and opposes the kinase MBK-2; meg-3/meg-4 loss is epistatic. PPTR-1 does part of the work as the regulatory subunit that targets PP2A to the MEG substrates, so the process annotation is a core one. Supporting Evidence: PMID:25535836 Phosphorylation of the MEGs promotes granule disassembly and dephosphorylation promotes granule assembly. PMID:21127218 We have identified a mutant (pptr-1) in which P granules become unstable during mitosis and P granule proteins and RNAs are distributed equally to somatic and germline blastomeres. |
| GO:1903863 P granule assembly | IMP PMID:25535836 Regulation of RNA granule dynamics by phosphorylation of ser... | ACCEPT | Summary: PP2A(PPTR-1) dephosphorylates MEG proteins to promote P granule assembly and stability in the zygote. Reason: In pptr-1 mutants zygote P granules fail to grow and disassemble at each division (PMID:21127218, PMID:25535836). PPTR-1 acts redundantly with PPTR-2 and opposes the kinase MBK-2; meg-3/meg-4 loss is epistatic. PPTR-1 does part of the work as the regulatory subunit that targets PP2A to the MEG substrates, so the process annotation is a core one. Supporting Evidence: PMID:25535836 Phosphorylation of the MEGs promotes granule disassembly and dephosphorylation promotes granule assembly. PMID:21127218 We have identified a mutant (pptr-1) in which P granules become unstable during mitosis and P granule proteins and RNAs are distributed equally to somatic and germline blastomeres. |
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Download this section (compressed HTML)Q: Which MEG phosphosites does PP2A(PPTR-1) dephosphorylate, and does PPTR-1 enrichment on P granules spatially bias granule condensation in the posterior?
Q: Does PPTR-1 dephosphorylate other insulin-pathway kinases (AKT-2, SGK-1) or only AKT-1?
Experiment: Reconstitute PAA-1/LET-92/PPTR-1 holoenzyme and test dephosphorylation of MBK-2-phosphorylated MEG-3 in vitro, with site-specific phosphoproteomics and phospho-site mutant MEG-3 rescue in pptr-1;pptr-2 embryos.
Hypothesis: PP2A(PPTR-1) directly dephosphorylates MBK-2 sites on MEG-3.
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