daf-2;pptr-1

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Genetic mutants with daf-2, pptr-1 alterations

Names of genes are ordered alphabetically. For the order of interventions, please see the specific paper.

Temperature °C
15
Diet
OP50
Lifespan (days)
29.8
Lifespan change (compared to wild type)
25.21%
Phenotype
Knockdown of pptr-1 resulted in a significant reduction in daf-2(e1370) lifespan
Lifespan comparisons
Double mutant daf-2(e1370);pptr-1(RNAi) has a lifespan of 29.8 days, while single mutant daf-2(e1370) has a lifespan of 38.9 days, single mutant pptr-1(RNAi) has a lifespan of 22.8 days and wild type has a lifespan of 23.8 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Padmanabhan S et al., 2009, A PP2A regulatory subunit regulates C. elegans insulin/IGF-1 signaling by modulating AKT-1 phosphorylation. Cell. 136(5):939-51 19249087 Click here to select all mutants from this PubMed ID in the graph
Abstract
The C. elegans insulin/IGF-1 signaling (IIS) cascade plays a central role in regulating life span, dauer, metabolism, and stress. The major regulatory control of IIS is through phosphorylation of its components by serine/threonine-specific protein kinases. 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. Modulation of pptr-1 affects IIS pathway-associated phenotypes including life span, dauer, stress resistance, and fat storage. We show that PPTR-1 functions by regulating worm AKT-1 phosphorylation at Thr 350. With striking conservation, mammalian B56beta regulates Akt phosphorylation at Thr 308 in 3T3-L1 adipocytes. In C. elegans, this ultimately leads to changes in subcellular localization and transcriptional activity of the forkhead transcription factor DAF-16. This study reveals a conserved role for the B56 regulatory subunit in regulating insulin signaling through AKT dephosphorylation, thereby having widespread implications in cancer and diabetes research.

Temperature °C
15
Diet
OP50
Lifespan (days)
30.5
Lifespan change (compared to wild type)
28.69%
Phenotype
Knockdown of pptr-1 resulted in a significant reduction in daf-2(e1370) lifespan
Lifespan comparisons
Double mutant daf-2(e1370);pptr-1(RNAi) has a lifespan of 30.5 days, while single mutant daf-2(e1370) has a lifespan of 35.9 days, single mutant pptr-1(RNAi) has a lifespan of 22.3 days and wild type has a lifespan of 23.7 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Padmanabhan S et al., 2009, A PP2A regulatory subunit regulates C. elegans insulin/IGF-1 signaling by modulating AKT-1 phosphorylation. Cell. 136(5):939-51 19249087 Click here to select all mutants from this PubMed ID in the graph
Abstract
The C. elegans insulin/IGF-1 signaling (IIS) cascade plays a central role in regulating life span, dauer, metabolism, and stress. The major regulatory control of IIS is through phosphorylation of its components by serine/threonine-specific protein kinases. 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. Modulation of pptr-1 affects IIS pathway-associated phenotypes including life span, dauer, stress resistance, and fat storage. We show that PPTR-1 functions by regulating worm AKT-1 phosphorylation at Thr 350. With striking conservation, mammalian B56beta regulates Akt phosphorylation at Thr 308 in 3T3-L1 adipocytes. In C. elegans, this ultimately leads to changes in subcellular localization and transcriptional activity of the forkhead transcription factor DAF-16. This study reveals a conserved role for the B56 regulatory subunit in regulating insulin signaling through AKT dephosphorylation, thereby having widespread implications in cancer and diabetes research.

Search genes: daf-2 pptr-1

Entrez ID
Symbol
GenAge
Wormbase ID

175410
daf-2
View on GenAge (daf-2)
WBGene00000898

Insulin-like receptor subunit beta;Receptor protein-tyrosine kinase;hypothetical protein

Locus: CELE_Y55D5A.5

Wormbase description: daf-2 encodes a receptor tyrosine kinase that is the C. elegans insulin/IGF receptor ortholog; DAF-2 activity is required for a number of processes in C. elegans, including embryonic and larval development, formation of the developmentally arrested dauer larval stage (diapause), larval developmental timing, adult longevity, reproduction, fat storage, salt chemotaxis learning, and stress resistance, including response to high temperature, oxidative stress, and bacterial infection; DAF-2 signals through a conserved PI 3-kinase pathway to negatively regulate the activity of DAF-16, a Forkhead-related transcription factor, by inducing its phosphorylation and nuclear exclusion; in addition, DAF-2 negatively regulates the nuclear localization, and hence transcriptional activity, of SKN-1 in intestinal nuclei; amongst the 38 predicted insulin-like molecules in C. elegans, genetic and microarray analyses suggest that at least DAF-28, INS-1, and INS-7 are likely DAF-2 ligands; genetic mosaic and tissue-specific promoter studies indicate that daf-2 can function cell nonautonomously and within multiple cell types to influence dauer formation and adult lifespan, likely by regulating the production of secondary endocrine signals that coordinate growth and longevity throughout the animal; temporal analysis of daf-2 function indicates that daf-2 regulates lifespan, reproduction, and diapause independently, at distinct times during the animal's life cycle.

Entrez ID
Symbol
GenAge
Wormbase ID

180100
pptr-1
View on GenAge (pptr-1)
WBGene00012348

Serine/threonine-protein phosphatase 2A regulatory subunit pptr-1

Locus: CELE_W08G11.4

Wormbase description: pptr-1 encodes a PP2A holoenzyme regulatory subunit, a member of the B56 family of genes homologous to mammalian PPP2R5B (OMIM: 601644); out of the seven PP2A regulatory subunits only pptr-1 regulates dauer formation downstream of daf-2;pptr-1 controls dauer formation specifically through the IIS pathway; pptr-1 regulates multiple phenotypes associated with the IIS pathways like stress resistance and life span; genetically pptr-1 is at the level of or downstream of akt-1 in IIS pathway; PPTR-1/mammalian B56beta regulatory subunit function to modulate AKT-1 phosphorylation in a conserved manner across phylogeny; changes in PPTR-1 levels affect the activity of AKT-1 and as a result, modulate DAF-16 subcellular localization; PPTR-1 positively regulates DAF-16 nuclear localization and thereby its activity on transcriptional targets; PPTR1 expression is predominantly cytosolic and overlaps with AKT-2 in pharynx, head neurons, nerve ring, spermathecae and vulva.

Orthologs of daf-2;pptr-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	InR;wdb
Mus musculus	Insr;Ppp2r5e
Mus musculus	Insr;Ppp2r5a
Mus musculus	Insr;Ppp2r5b
Mus musculus	Igf1r;Ppp2r5e
Mus musculus	Igf1r;Ppp2r5a
Mus musculus	Igf1r;Ppp2r5b
Mus musculus	Insrr;Ppp2r5e
Mus musculus	Insrr;Ppp2r5a
Mus musculus	Insrr;Ppp2r5b
Mus musculus	Ppp2r5e;Insr
Mus musculus	Ppp2r5e;Igf1r
Mus musculus	Ppp2r5e;Insrr
Mus musculus	Ppp2r5a;Insr
Mus musculus	Ppp2r5a;Igf1r
Mus musculus	Ppp2r5a;Insrr
Mus musculus	Ppp2r5b;Insr
Mus musculus	Ppp2r5b;Igf1r
Mus musculus	Ppp2r5b;Insrr

Orthologs of daf-2 in SynergyAge

Show in SynergyAge
Species	Gene
Drosophila melanogaster	InR

Not in SynergyAge
Species	Gene
Mus musculus	Insr
Mus musculus	Igf1r
Mus musculus	Insrr

Orthologs of pptr-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	wdb
Mus musculus	Ppp2r5e
Mus musculus	Ppp2r5a
Mus musculus	Ppp2r5b