akt-1;sdf-9

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Genetic mutants with akt-1, sdf-9 alterations

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

Temperature °C
25
Diet
NGM
Lifespan (days)
15.0
Lifespan change (compared to wild type)
15.38%
Lifespan comparisons
Double mutant akt-1(mg306);sdf-9(mg227) has a lifespan of 15.0 days, while single mutant sdf-9(mg227) has a lifespan of 13.75 days, single mutant akt-1(mg306) has a lifespan of 15.0 days and wild type has a lifespan of 13.0 days.
Type of interaction
See methods
Dependent
Citation
View abstract
Hu PJ et al., 2006, Two membrane-associated tyrosine phosphatase homologs potentiate C. elegans AKT-1/PKB signaling. PLoS Genet. 2(7):e99 16839187 Click here to select all mutants from this PubMed ID in the graph
Abstract
Akt/protein kinase B (PKB) functions in conserved signaling cascades that regulate growth and metabolism. In humans, Akt/PKB is dysregulated in diabetes and cancer; in Caenorhabditis elegans, Akt/PKB functions in an insulin-like signaling pathway to regulate larval development. To identify molecules that modulate C. elegans Akt/PKB signaling, we performed a genetic screen for enhancers of the akt-1 mutant phenotype (eak). We report the analysis of three eak genes. eak-6 and eak-5/sdf-9 encode protein tyrosine phosphatase homologs; eak-4 encodes a novel protein with an N-myristoylation signal. All three genes are expressed primarily in the two endocrine XXX cells, and their predicted gene products localize to the plasma membrane. Genetic evidence indicates that these proteins function in parallel to AKT-1 to inhibit the FoxO transcription factor DAF-16. These results define two membrane-associated protein tyrosine phosphatase homologs that may potentiate C. elegans Akt/PKB signaling by cell autonomous and cell nonautonomous mechanisms. Similar molecules may modulate Akt/PKB signaling in human endocrine tissues.

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

Temperature °C
20
Lifespan (days)
13.0
Lifespan change (compared to wild type)
2.36%
Phenotype
Double mutants had lifespans comparable to WT.
Lifespan comparisons
Double mutant akt-1(mg306);sdf-9(mg337) has a lifespan of 13.0 days, while single mutant sdf-9(mg337) has a lifespan of 12.9 days, single mutant akt-1(mg306) has a lifespan of 13.7 days and wild type has a lifespan of 12.7 days.
Type of interaction
See methods
Dependent
Citation
View abstract
Zhang Y et al., 2008, Caenorhabditis elegans EAK-3 inhibits dauer arrest via nonautonomous regulation of nuclear DAF-16/FoxO activity. Dev Biol. 315(2):290-302 18241854 Click here to select all mutants from this PubMed ID in the graph
Abstract
Insulin regulates development, metabolism, and lifespan via a conserved PI3K/Akt pathway that promotes cytoplasmic sequestration of FoxO transcription factors. The regulation of nuclear FoxO is poorly understood. In the nematode Caenorhabditis elegans, insulin-like signaling functions in larvae to inhibit dauer arrest and acts during adulthood to regulate lifespan. In a screen for genes that modulate C. elegans insulin-like signaling, we identified eak-3, which encodes a novel protein that is specifically expressed in the two endocrine XXX cells. The dauer arrest phenotype of eak-3 mutants is fully suppressed by mutations in daf-16/FoxO, which encodes the major target of C. elegans insulin-like signaling, and daf-12, which encodes a nuclear receptor regulated by steroid hormones known as dafachronic acids. eak-3 mutation does not affect DAF-16/FoxO subcellular localization but enhances expression of the direct DAF-16/FoxO target sod-3 in a daf-16/FoxO- and daf-12-dependent manner. eak-3 mutants have normal lifespans, suggesting that EAK-3 decouples insulin-like regulation of development and longevity. We propose that EAK-3 activity in the XXX cells promotes the synthesis and/or secretion of a hormone that acts in parallel to AKT-1 to inhibit the expression of DAF-16/FoxO target genes. Similar hormonal pathways may regulate FoxO target gene expression in mammals.

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

Temperature °C
25
Diet
NGM
Lifespan (days)
13.5
Lifespan change (compared to wild type)
3.85%
Lifespan comparisons
Double mutant akt-1(mg306);sdf-9(ut187) has a lifespan of 13.5 days, while single mutant sdf-9(ut187) has a lifespan of 13.75 days, single mutant akt-1(mg306) has a lifespan of 15.0 days and wild type has a lifespan of 13.0 days.
Type of interaction
See methods
Antagonistic (positive)
Citation
View abstract
Hu PJ et al., 2006, Two membrane-associated tyrosine phosphatase homologs potentiate C. elegans AKT-1/PKB signaling. PLoS Genet. 2(7):e99 16839187 Click here to select all mutants from this PubMed ID in the graph
Abstract
Akt/protein kinase B (PKB) functions in conserved signaling cascades that regulate growth and metabolism. In humans, Akt/PKB is dysregulated in diabetes and cancer; in Caenorhabditis elegans, Akt/PKB functions in an insulin-like signaling pathway to regulate larval development. To identify molecules that modulate C. elegans Akt/PKB signaling, we performed a genetic screen for enhancers of the akt-1 mutant phenotype (eak). We report the analysis of three eak genes. eak-6 and eak-5/sdf-9 encode protein tyrosine phosphatase homologs; eak-4 encodes a novel protein with an N-myristoylation signal. All three genes are expressed primarily in the two endocrine XXX cells, and their predicted gene products localize to the plasma membrane. Genetic evidence indicates that these proteins function in parallel to AKT-1 to inhibit the FoxO transcription factor DAF-16. These results define two membrane-associated protein tyrosine phosphatase homologs that may potentiate C. elegans Akt/PKB signaling by cell autonomous and cell nonautonomous mechanisms. Similar molecules may modulate Akt/PKB signaling in human endocrine tissues.

Temperature °C
20
Lifespan (days)
12.7
Phenotype
Double mutants had lifespans comparable to WT.
Lifespan comparisons
Double mutant akt-1(mg306);sdf-9(ut187) has a lifespan of 12.7 days, while single mutant sdf-9(ut187) has a lifespan of 12.9 days, single mutant akt-1(mg306) has a lifespan of 13.7 days and wild type has a lifespan of 12.7 days.
Type of interaction
See methods
Antagonistic (positive)
Citation
View abstract
Zhang Y et al., 2008, Caenorhabditis elegans EAK-3 inhibits dauer arrest via nonautonomous regulation of nuclear DAF-16/FoxO activity. Dev Biol. 315(2):290-302 18241854 Click here to select all mutants from this PubMed ID in the graph
Abstract
Insulin regulates development, metabolism, and lifespan via a conserved PI3K/Akt pathway that promotes cytoplasmic sequestration of FoxO transcription factors. The regulation of nuclear FoxO is poorly understood. In the nematode Caenorhabditis elegans, insulin-like signaling functions in larvae to inhibit dauer arrest and acts during adulthood to regulate lifespan. In a screen for genes that modulate C. elegans insulin-like signaling, we identified eak-3, which encodes a novel protein that is specifically expressed in the two endocrine XXX cells. The dauer arrest phenotype of eak-3 mutants is fully suppressed by mutations in daf-16/FoxO, which encodes the major target of C. elegans insulin-like signaling, and daf-12, which encodes a nuclear receptor regulated by steroid hormones known as dafachronic acids. eak-3 mutation does not affect DAF-16/FoxO subcellular localization but enhances expression of the direct DAF-16/FoxO target sod-3 in a daf-16/FoxO- and daf-12-dependent manner. eak-3 mutants have normal lifespans, suggesting that EAK-3 decouples insulin-like regulation of development and longevity. We propose that EAK-3 activity in the XXX cells promotes the synthesis and/or secretion of a hormone that acts in parallel to AKT-1 to inhibit the expression of DAF-16/FoxO target genes. Similar hormonal pathways may regulate FoxO target gene expression in mammals.

Search genes: akt-1 sdf-9

Entrez ID
Symbol
GenAge
Wormbase ID

179424
akt-1
View on GenAge (akt-1)
WBGene00000102

Serine/threonine-protein kinase akt-1

Locus: CELE_C12D8.10

Wormbase description: akt-1 encodes an ortholog of the serine/threonine kinase Akt/PKB; akt-1 genetically interacts with the insulin signaling pathway and functions to regulate such processes as dauer larval development and salt chemotaxis learning; AKT-1 binds calmodulin in vitro in a calcium-dependent manner; an AKT-1::GFP fusion protein is widely expressed beginning in late stage embryos and continuing through adulthood; expression is seen in head, tail, and dorsal and ventral cord neurons, with additional expression seen in other cells including those of the pharynx, hypodermis, intestine, and spermatheca; two alleles of akt-1 (sa573 and sa700) have a Daf-c mutant phenotype at 27 degrees C (Hid phenotype).

Entrez ID
Symbol
GenAge
Wormbase ID

189901
sdf-9
View on GenAge (sdf-9)
WBGene00004748

Protein sdf-9

Locus: CELE_Y44A6D.4

Wormbase description: sdf-9 encodes a protein tyrosine phosphatase, paralogous to EAK-6; sdf-9 acts in parallel to akt-1 to regulate insulin-like signaling and dauer formation and may promote DAF-9 activity by means of steroid hormone signalling; sdf-9 dauer larvae resemble those of daf-9 and daf-12 dauer-constitutive mutants, and these Daf-c mutants are all enhanced by cholesterol deprivation; SDF-9 is expressed in the neuroendocrine XXXL/R cells, where it associates with the plasma membrane; ablation of the XXXL/R cells in wild-type L1 larvae also causes daf-9-like pseudodauer larvae.

Orthologs of akt-1;sdf-9 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene

Orthologs of akt-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Akt1
Mus musculus	Akt1
Mus musculus	Akt2
Mus musculus	Akt3

Orthologs of sdf-9 in SynergyAge

Show in SynergyAge
Species	Gene