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PMID: 10995457 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Modulation of Akt kinase activity by binding to Hsp90.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 97 ·No. 20 ·2000-09-26 ·Pages 10832-7

Sato S, Fujita N, Tsuruo T

Abstract

Serine/threonine kinase Akt/PKB is a downstream effector molecule of phosphoinositide 3-kinase and is thought to mediate many biological actions toward anti-apoptotic responses. We found that Akt formed a complex with a 90-kDa heat-shock protein (Hsp90) in vivo. By constructing deletion mutants, we identified that amino acid residues 229-309 of Akt were involved in the binding to Hsp90 and amino acid residues 327-340 of Hsp90beta were involved in the binding to Akt. Inhibition of Akt-Hsp90 binding led to the dephosphorylation and inactivation of Akt, which increased sensitivity of the cells to apoptosis-inducing stimulus. The dephosphorylation of Akt was caused by an increase in protein phosphatase 2A (PP2A)-mediated dephosphorylation and not by a decrease in 3-phosphoinositide-dependent protein kinase-1-mediated phosphorylation. These results indicate that Hsp90 plays an important role in maintaining Akt kinase activity by preventing PP2A-mediated dephosphorylation.

MeSH Terms
Cell Line Enzyme Activation HSP90 Heat-Shock Proteins/metabolism Humans Phosphatidylinositol 3-Kinases/metabolism Protein Binding Protein Serine-Threonine Kinases/metabolism Signal Transduction
Chemicals
HSP90 Heat-Shock Proteins Protein Serine-Threonine Kinases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Sato S
Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo 113-0032, Japan.
Fujita N
Tsuruo T
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32 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.170276797
Published
2000-09-26
Pages
10832-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC27109
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.170276797 PMC Full Text View journal details
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