akt-1;akt-2

There is no network for this step.

Fullscreen mode

Hide graph

Legend

Genetic mutants with akt-1, akt-2 alterations

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

Temperature °C
25
Diet
OP50
Lifespan (days)
20.4
Citation
View abstract
Thyagarajan B et al., 2010, ETS-4 is a transcriptional regulator of life span in Caenorhabditis elegans. PLoS Genet. 6(9):e1001125 20862312 Click here to select all mutants from this PubMed ID in the graph
Abstract
Aging is a complex phenotype responsive to a plethora of environmental inputs; yet only a limited number of transcriptional regulators are known to influence life span. How the downstream expression programs mediated by these factors (or others) are coordinated into common or distinct set of aging effectors is an addressable question in model organisms, such as C. elegans. Here, we establish the transcription factor ETS-4, an ortholog of vertebrate SPDEF, as a longevity determinant. Adult worms with ets-4 mutations had a significant extension of mean life span. Restoring ETS-4 activity in the intestine, but not neurons, of ets-4 mutant worms rescued life span to wild-type levels. Using RNAi, we demonstrated that ets-4 is required post-developmentally to regulate adult life span; thus uncoupling the role of ETS-4 in aging from potential functions in worm intestinal development. Seventy ETS-4-regulated genes, identified by gene expression profiling of two distinct ets-4 alleles and analyzed by bioinformatics, were enriched for known longevity effectors that function in lipid transport, lipid metabolism, and innate immunity. Putative target genes were enriched for ones that change expression during normal aging, the majority of which are controlled by the GATA factors. Also, some ETS-4-regulated genes function downstream of the FOXO factor, DAF-16 and the insulin/IGF-1 signaling pathway. However, epistasis and phenotypic analyses indicate that ets-4 functioned in parallel to the insulin/IGF-1 receptor, daf-2 and akt-1/2 kinases. Furthermore, ets-4 required daf-16 to modulate aging, suggesting overlap in function at the level of common targets that affect life span. In conclusion, ETS-4 is a new transcriptional regulator of aging, which shares transcriptional targets with GATA and FOXO factors, suggesting that overlapping pathways direct common sets of lifespan-related genes.

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

Temperature °C
25
Lifespan (days)
17.5
Lifespan change (compared to wild type)
19.05%
Lifespan comparisons
Double mutant akt-1(RNAi);akt-2(ok393) has a lifespan of 17.5 days, while wild type has a lifespan of 14.7 days.
Type of interaction
See methods
Contains dependence
Citation
View abstract
Hertweck M et al., 2004, C. elegans SGK-1 is the critical component in the Akt/PKB kinase complex to control stress response and life span. Dev Cell. 6(4):577-88 15068796 Click here to select all mutants from this PubMed ID in the graph
Abstract
The DAF-2 insulin receptor-like signaling pathway controls metabolism, development, longevity, and stress response in C. elegans. Here we show that SGK-1, the C. elegans homolog of the serum- and glucocorticoid-inducible kinase SGK, acts in parallel to the AKT kinases to mediate DAF-2 signaling. Loss of sgk-1 results in defective egg-laying, extended generation time, increased stress resistance, and an extension of life span. SGK-1 forms a protein complex with the AKT kinases, and is activated by and strictly depends on PDK-1. All three kinases of this complex are able to directly phosphorylate DAF-16/FKHRL1, yet have different functions in DAF-2 signaling. Whereas AKT-1 and AKT-2 are more important for regulating dauer formation, SGK-1 is the crucial factor for the control of development, stress response, and longevity. Our data also suggest the existence of a second pathway from DAF-2 to DAF-16 that does not depend on AKT-1, AKT-2, and SGK-1.

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

Diet
OP50
Lifespan (days)
48.1
Lifespan change (compared to wild type)
220.67%
Phenotype
Akt-1;akt-2 double mutants are extremely long-lived compared to single mutants.
Lifespan comparisons
Double mutant akt-1(mg306);akt-2(ok393) has a lifespan of 48.1 days, while single mutant akt-2(ok393) has a lifespan of 19.1 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
Synergistic (positive)
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.

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

Temperature °C
20
Lifespan (days)
34.2
Lifespan change (compared to wild type)
129.53%
Lifespan comparisons
Double mutant akt-1(ok525);akt-2(ok393) has a lifespan of 34.2 days, while wild type has a lifespan of 14.9 days.
Citation
View abstract
Oh SW et al., 2005, JNK regulates lifespan in Caenorhabditis elegans by modulating nuclear translocation of forkhead transcription factor/DAF-16. Proc Natl Acad Sci U S A. 102(12):4494-9 15767565 Click here to select all mutants from this PubMed ID in the graph
Abstract
DAF-16/forkhead transcription factor, the downstream target of the insulin-like signaling in Caenorhabditis elegans, is indispensable for both lifespan regulation and stress resistance. Here, we demonstrate that c-Jun N-terminal kinase (JNK) is a positive regulator of DAF-16 in both processes. Our genetic analysis suggests that the JNK pathway acts in parallel with the insulin-like signaling pathway to regulate lifespan and both pathways converge onto DAF-16. We also show that JNK-1 directly interacts with and phosphorylates DAF-16. Moreover, in response to heat stress, JNK-1 promotes the translocation of DAF-16 into the nucleus. Our findings define an interaction between two well conserved proteins, JNK-1 and DAF-16, and provide a mechanism by which JNK regulates longevity and stress resistance.

Temperature °C
25
Lifespan (days)
17.5
Lifespan change (compared to wild type)
19.05%
Phenotype
Individual inactivation of neither akt-1 nor akt-2 had an effect on longevity (Table 2), and akt-1(RNAi);akt-2(ok393) animals only showed a weak life span extension by 19%. This suggests that, in contrast to their strong input into dauer regulation, neither akt-1 nor akt-2 plays a major role in the control of life span.
Lifespan comparisons
Double mutant akt-1(ok525);akt-2(ok393) has a lifespan of 17.5 days, while single mutant akt-2(ok393) has a lifespan of 14.2 days, single mutant akt-1(ok525) has a lifespan of 15.5 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
Hertweck M et al., 2004, C. elegans SGK-1 is the critical component in the Akt/PKB kinase complex to control stress response and life span. Dev Cell. 6(4):577-88 15068796 Click here to select all mutants from this PubMed ID in the graph
Abstract
The DAF-2 insulin receptor-like signaling pathway controls metabolism, development, longevity, and stress response in C. elegans. Here we show that SGK-1, the C. elegans homolog of the serum- and glucocorticoid-inducible kinase SGK, acts in parallel to the AKT kinases to mediate DAF-2 signaling. Loss of sgk-1 results in defective egg-laying, extended generation time, increased stress resistance, and an extension of life span. SGK-1 forms a protein complex with the AKT kinases, and is activated by and strictly depends on PDK-1. All three kinases of this complex are able to directly phosphorylate DAF-16/FKHRL1, yet have different functions in DAF-2 signaling. Whereas AKT-1 and AKT-2 are more important for regulating dauer formation, SGK-1 is the crucial factor for the control of development, stress response, and longevity. Our data also suggest the existence of a second pathway from DAF-2 to DAF-16 that does not depend on AKT-1, AKT-2, and SGK-1.

Search genes: akt-1 akt-2

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

181524
akt-2
View on GenAge (akt-2)
WBGene00000103

Serine/threonine-protein kinase akt-2

Locus: CELE_F28H6.1

Wormbase description: akt-2 encodes a homolog of the serine/threonine kinase Akt/PKB, AKT-2, that is required for progression through the dauer stage of development and for the negative regulation of adult lifespan; inactivation of akt-2 causes animals to arrest constitutively at the dauer stage, while having an increased life span; widely expressed, AKT-2 is activated by the phospholipid products of phosphoinositide 3-kinase AGE-1/PI3K and by PDK-1, a homolog of vertebrate 3-phosphoinositide-dependent kinase-1 (PDK-1) Normal akt-2 (and akt-1) activity is required for excess pdk-1 activity to suppress the dauer-arrest phenotype of age-1, indicating that the 3-phosphoinositide-dependent kinase-1 homolog PDK-1 transduces signals from AGE-1 to AKT-2 (and AKT-1); conversely, the akt-2 loss-of-function phenotype is suppressed by daf-16 null mutations, indicating that the Fork head transcription factor DAF-16 is downstream of AKT-2 (and AKT-1), and that AKT-1 and AKT-2 act primarily to antagonize DAF-16.

Orthologs of akt-1;akt-2 in SynergyAge

Show in SynergyAge
Species	Gene

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

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 akt-2 in SynergyAge

Show in SynergyAge
Species	Gene

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