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

Dev Cell. 2004 Apr;6(4):577-88. doi: 10.1016/s1534-5807(04)00095-4.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Phosphoinositide-Dependent Protein Kinases
  • Animals
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / 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
  • Protein-Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-akt
  • Receptor, Insulin / genetics
  • Receptor, Insulin / metabolism*
  • Signal Transduction / genetics
  • Stress, Physiological / genetics
  • Stress, Physiological / metabolism*

Substances

  • Caenorhabditis elegans Proteins
  • Immediate-Early Proteins
  • Insulin
  • Macromolecular Substances
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • DAF-2 protein, C elegans
  • Receptor, Insulin
  • 3-Phosphoinositide-Dependent Protein Kinases
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • akt-2 protein, C elegans
  • serum-glucocorticoid regulated kinase