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PMID: 11154276 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

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

Molecular and cellular biology ·Vol. 21 ·No. 3 ·2001-02-00 ·Pages 893-901

Kim AH, Khursigara G, Sun X, Franke TF, Chao MV

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.

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/chemistry,genetics,metabolism Mitogen-Activated Protein Kinases/metabolism Phosphatidylinositol 3-Kinases/metabolism Phosphorylation Protein Serine-Threonine Kinases Proto-Oncogene Proteins/metabolism Proto-Oncogene Proteins c-akt Serine/chemistry Signal Transduction Substrate Specificity
Chemicals
Proto-Oncogene Proteins Serine AKT1 protein, human Protein Serine-Threonine Kinases Proto-Oncogene Proteins c-akt JNK Mitogen-Activated Protein Kinases Mitogen-Activated Protein Kinases MAP Kinase Kinase Kinase 5 MAP Kinase Kinase Kinases MAP3K5 protein, human
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Kim A H
Molecular Neurobiology Program, Skirball Institute for Biomolecular Medicine, New York University School of Medicine, New York, New York 10016, USA.
Khursigara G
Sun X
Franke T F
Chao M V
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.21.3.893-901.2001
Published
2001-02-00
Pages
893-901
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC86680
Subset
IM
Grants
NINDS NIH HHS · R01 NS021072 · United States
NINDS NIH HHS · R56 NS021072 · United States
NINDS NIH HHS · NS21072 · United States
External Links
PubMed source DOI: 10.1128/MCB.21.3.893-901.2001 PMC Full Text View journal details
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