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Akt (protein kinase B) negatively regulates SEK1 by means of protein phosphorylation.

The protein serine-threonine kinase Akt mediates cell survival signaling initiated by various growth-promoting factors such as insulin. Here we report that SEK1 is a target of Akt in intact cells. Insulin inhibited the anisomycin-induced stimulation of both endogenous SEK1 and its substrate c-Jun N-terminal kinase (JNK), but not that of the upstream kinase MEKK1, in 293T cells. The inhibitory action of insulin on SEK1 or JNK1 activation was prevented by the phosphatidylinositol 3-kinase inhibitor LY294002. Expression of a constitutively active form of Akt also inhibited both SEK1 and JNK1 activation, but not that of MEKK1, in transfected 293T cells. Co-immunoprecipitation analysis revealed that endogenous Akt physically interacted with endogenous SEK1 in cells and that this interaction was promoted by insulin. In vitro and in vivo (32)P labeling indicated that Akt phosphorylated SEK1 on serine 78. The SEK1 mutant SEK1(S78A) was resistant to Akt-induced inhibition. Finally, activated Akt inhibited SEK1-mediated apoptosis, and this effect of Akt was prevented by overexpression of SEK(S78A). Taken together, these results suggest that Akt suppresses stress-activated signaling by targeting SEK1.

Pubmed ID: 11707464

Authors

  • Park HS
  • Kim MS
  • Huh SH
  • Park J
  • Chung J
  • Kang SS
  • Choi EJ

Journal

The Journal of biological chemistry

Publication Data

January 25, 2002

Associated Grants

None

Mesh Terms

  • Anisomycin
  • Apoptosis
  • Cell Line
  • Cell Survival
  • Chromones
  • Electrophoresis, Polyacrylamide Gel
  • Enzyme Activation
  • Enzyme Inhibitors
  • Glutathione Transferase
  • HeLa Cells
  • Humans
  • Immunoblotting
  • Insulin
  • JNK Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 4
  • MAP Kinase Kinase Kinase 1
  • Mitogen-Activated Protein Kinase Kinases
  • Mitogen-Activated Protein Kinases
  • Morpholines
  • Mutagenesis, Site-Directed
  • Phosphatidylinositol 3-Kinases
  • Phosphorylation
  • Precipitin Tests
  • Protein Binding
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-akt
  • Serine
  • Signal Transduction
  • Time Factors
  • Transfection