C. elegans SGK-1 is the critical component in the Akt/PKB kinase complex to control stress response and life span

被引:258
作者
Hertweck, M
Göbel, C
Baumeister, R [1 ]
机构
[1] Univ Freiburg, D-79104 Freiburg, Germany
[2] Univ Munich, Mol Neurogenet Lab, D-80336 Munich, Germany
基金
美国国家卫生研究院;
关键词
D O I
10.1016/S1534-5807(04)00095-4
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:577 / 588
页数:12
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