Authors: Hertweck M; Göbel C; Baumeister R
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.
Keywords: Animals; Caenorhabditis elegans/genetics/*metabolism; Caenorhabditis elegans Proteins/genetics/metabolism; Gene Expression Regulation, Developmental/genetics; Immediate-Early Proteins; Insulin/metabolism; Longevity/*genetics; Macromolecular Substances; Mutation/genetics; *Nuclear Proteins; Phenotype; Phosphorylation; Protein-Serine-Threonine Kinases/genetics/*metabolism; Proto-Oncogene Proteins/genetics/*metabolism; Proto-Oncogene Proteins c-akt; Receptor, Insulin/genetics/*metabolism; Signal Transduction/genetics; Stress, Physiological/genetics/*metabolism|
Journal: Developmental cell Volume: 6 Issue: 4 Pages: 577-88 Date: April 8, 2004 PMID: 15068796 |
Hertweck M, Göbel C, Baumeister R (2004) C. elegans SGK-1 is the critical component in the Akt/PKB kinase complex to control stress response and life span. Developmental cell 6: 577-88.
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