C. elegans SGK-1 is the critical component in the Akt/PKB kinase complex to control stress response and life span.
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.
Hertweck
Maren
M
BioIII, Bioinformatics and Molecular Genetics, University of Freiburg, D-79104 Freiburg, Germany.
Göbel
Christine
C
Baumeister
Ralf
R
D064413:3-Phosphoinositide-Dependent Protein Kinases; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D017874:Immediate-Early Proteins; D007328:Insulin / Q000378:metabolism; D008136:Longevity / Q000235:genetics*; D046911:Macromolecular Substances; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins; D010641:Phenotype; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D013312:Stress, Physiological / Q000235:genetics / Q000378:metabolism*; D000099184:Serum-Glucocorticoid Regulated Kinases
D064413:3-Phosphoinositide-Dependent Protein Kinases; D029742:Caenorhabditis elegans Proteins; D017874:Immediate-Early Proteins; D007328:Insulin; D046911:Macromolecular Substances; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D011972:Receptor, Insulin; D000099184:Serum-Glucocorticoid Regulated Kinases; C107483:DAF-2 protein, C elegans; C494916:akt-2 protein, C elegans