Akt phosphorylates and negatively regulates apoptosis signal-regulating kinase 1

A. H. Kim, G. Khursigara, X. Sun, T. F. Franke, M. V. Chao

Research output: Contribution to journalArticle

580 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)893-901
Number of pages9
JournalMolecular and cellular biology
Volume21
Issue number3
DOIs
StatePublished - Feb 8 2001
Externally publishedYes

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