akt-1;sgk-1

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Genetic mutants with akt-1, sgk-1 alterations

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

Temperature °C
20
Diet
OP50
Lifespan (days)
24.5
Lifespan change (compared to wild type)
20.69%
Phenotype
sgk-1(gf) did not extend the lifespan of akt-1(null) animals.
Lifespan comparisons
Double mutant akt-1(mg306);sgk-1(ft15) has a lifespan of 24.5 days, while single mutant sgk-1(ft15) has a lifespan of 21.9 days, single mutant akt-1(mg306) has a lifespan of 24.1 days and wild type has a lifespan of 20.3 days.
Type of interaction
See methods
Almost additive (positive)
Citation
View abstract
Chen AT et al., 2013, Effects of Caenorhabditis elegans sgk-1 mutations on lifespan, stress resistance, and DAF-16/FoxO regulation. Aging Cell. 12(5):932-40 23786484 Click here to select all mutants from this PubMed ID in the graph
Abstract
The AGC family serine-threonine kinases Akt and Sgk are similar in primary amino acid sequence and in vitro substrate specificity, and both kinases are thought to directly phosphorylate and inhibit FoxO transcription factors. In the nematode Caenorhabditis elegans, it is well established that AKT-1 controls dauer arrest and lifespan by regulating the subcellular localization of the FoxO transcription factor DAF-16. SGK-1 is thought to act similarly to AKT-1 in lifespan control by phosphorylating and inhibiting the nuclear translocation of DAF-16/FoxO. Using sgk-1 null and gain-of-function mutants, we now provide multiple lines of evidence indicating that AKT-1 and SGK-1 influence C. elegans lifespan, stress resistance, and DAF-16/FoxO activity in fundamentally different ways. Whereas AKT-1 shortens lifespan, SGK-1 promotes longevity in a DAF-16-/FoxO-dependent manner. In contrast to AKT-1, which reduces resistance to multiple stresses, SGK-1 promotes resistance to oxidative stress and ultraviolet radiation but inhibits thermotolerance. Analysis of several DAF-16/FoxO target genes that are repressed by AKT-1 reveals that SGK-1 represses a subset of these genes while having little influence on the expression of others. Accordingly, unlike AKT-1, which promotes the cytoplasmic sequestration of DAF-16/FoxO, SGK-1 does not influence DAF-16/FoxO subcellular localization. Thus, in spite of their similar in vitro substrate specificities, Akt and Sgk influence longevity, stress resistance, and FoxO activity through distinct mechanisms in vivo. Our findings highlight the need for a re-evaluation of current paradigms of FoxO regulation by Sgk.

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

Diet
OP50
Lifespan (days)
11.0
Lifespan change (compared to wild type)
-25.17%
Phenotype
Sgk-1 activity is required for lifespan extension in akt-1 null mutants.
Lifespan comparisons
Double mutant akt-1(mg306);sgk-1(mg455) has a lifespan of 11.0 days, while single mutant sgk-1(mg455) has a lifespan of 9.4 days, single mutant akt-1(mg306) has a lifespan of 26.5 days and wild type has a lifespan of 14.7 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Alam H et al., 2010, EAK-7 controls development and life span by regulating nuclear DAF-16/FoxO activity. Cell Metab. 12(1):30-41 20620993 Click here to select all mutants from this PubMed ID in the graph
Abstract
FoxO transcription factors control development and longevity in diverse species. Although FoxO regulation via changes in its subcellular localization is well established, little is known about how FoxO activity is regulated in the nucleus. Here, we show that the conserved C. elegans protein EAK-7 acts in parallel to the serine/threonine kinase AKT-1 to inhibit the FoxO transcription factor DAF-16. Loss of EAK-7 activity promotes diapause and longevity in a DAF-16/FoxO-dependent manner. Whereas akt-1 mutation activates DAF-16/FoxO by promoting its translocation from the cytoplasm to the nucleus, eak-7 mutation increases nuclear DAF-16/FoxO activity without influencing DAF-16/FoxO subcellular localization. Thus, EAK-7 and AKT-1 inhibit DAF-16/FoxO activity via distinct mechanisms. Our results implicate EAK-7 as a FoxO regulator and highlight the biological impact of a regulatory pathway that governs the activity of nuclear FoxO without altering its subcellular location.

Diet
OP50
Lifespan (days)
14.2
Lifespan change (compared to wild type)
-5.33%
Phenotype
Sgk-1 activity is required for lifespan extension in akt-1 null mutants.
Lifespan comparisons
Double mutant akt-1(mg306);sgk-1(mg455) has a lifespan of 14.2 days, while single mutant sgk-1(mg455) has a lifespan of 10.2 days, single mutant akt-1(mg306) has a lifespan of 21.3 days and wild type has a lifespan of 15.0 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Alam H et al., 2010, EAK-7 controls development and life span by regulating nuclear DAF-16/FoxO activity. Cell Metab. 12(1):30-41 20620993 Click here to select all mutants from this PubMed ID in the graph
Abstract
FoxO transcription factors control development and longevity in diverse species. Although FoxO regulation via changes in its subcellular localization is well established, little is known about how FoxO activity is regulated in the nucleus. Here, we show that the conserved C. elegans protein EAK-7 acts in parallel to the serine/threonine kinase AKT-1 to inhibit the FoxO transcription factor DAF-16. Loss of EAK-7 activity promotes diapause and longevity in a DAF-16/FoxO-dependent manner. Whereas akt-1 mutation activates DAF-16/FoxO by promoting its translocation from the cytoplasm to the nucleus, eak-7 mutation increases nuclear DAF-16/FoxO activity without influencing DAF-16/FoxO subcellular localization. Thus, EAK-7 and AKT-1 inhibit DAF-16/FoxO activity via distinct mechanisms. Our results implicate EAK-7 as a FoxO regulator and highlight the biological impact of a regulatory pathway that governs the activity of nuclear FoxO without altering its subcellular location.

Search genes: akt-1 sgk-1

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

181697
sgk-1
View on GenAge (sgk-1)
WBGene00004789

Serine/threonine-protein kinase sgk-1

Locus: CELE_W10G6.2

Wormbase description: sgk-1 encodes a serine/threonine protein kinase that is orthologous to the mammalian serum- and glucocorticoid-inducible kinases (SGKs); in C. elegans, sgk-1 activity is required for normal egg laying, generation time, stress response, and adult life span; SGK-1 forms a complex with the AKT kinases with which it functions in parallel to mediate certain aspects of DAF-2/insulin-signaling; SGK-1 phosphorylates DAF-16 in vitro in a manner strictly dependent upon pdk-1 which encodes a 3-phosphoinositide-dependent kinase; an SGK-1::GFP fusion protein is expressed beginning in late embryonic stages and in larvae is seen in sensory and motor neurons as well as in the intestine; in neurons SGK-1::GFP localizes to the cytoplasm and the nucleus, while in the intestine SGK-1::GFP is found exclusively in the cytoplasm.

Orthologs of akt-1;sgk-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Akt1;Sgk3
Mus musculus	Akt1;Sgk2
Mus musculus	Akt1;Sgk1
Mus musculus	Akt2;Sgk3
Mus musculus	Akt2;Sgk2
Mus musculus	Akt2;Sgk1
Mus musculus	Akt3;Sgk3
Mus musculus	Akt3;Sgk2
Mus musculus	Akt3;Sgk1

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 sgk-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Sgk3
Mus musculus	Sgk2
Mus musculus	Sgk1