Akt phosphorylates and negatively regulates apoptosis signal-regulating kinase 1.

The Akt family of serine/threonine-directed kinases promotes cellular survival in part by phosphorylating and inhibiting death-inducing proteins. Here we describe a novel functional interaction between Akt and apoptosis signal-regulating kinase 1 (ASK1), a mitogen-activated protein kinase kinase kinase. Akt decreased ASK1 kinase activity stimulated by both oxidative stress and overexpression ...
in 293 cells by phosphorylating a consensus Akt site at serine 83 of ASK1. Activation of the phosphoinositide 3-kinase (PI3-K)/Akt pathway also inhibited the serum deprivation-induced activity of endogenous ASK1 in L929 cells. An association between Akt and ASK1 was detected in cells by coimmunoprecipitation. Phosphorylation by Akt inhibited ASK1-mediated c-Jun N-terminal kinase and activating transcription factor 2 activities in intact cells. Finally, activation of the PI3-K/Akt pathway reduced apoptosis induced by ASK1 in a manner dependent on phosphorylation of serine 83 of ASK1. These results provide the first direct link between Akt and the family of stress-activated kinases.
Mesh Terms:
Amino Acid Sequence, Apoptosis, Cell Line, Cell Survival, HeLa Cells, Humans, JNK Mitogen-Activated Protein Kinases, MAP Kinase Kinase Kinase 5, MAP Kinase Kinase Kinases, Mitogen-Activated Protein Kinases, Phosphatidylinositol 3-Kinases, Phosphorylation, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-akt, Serine, Signal Transduction, Substrate Specificity
Mol. Cell. Biol.
Date: Feb. 01, 2001
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