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Modulation of Akt kinase activity by binding to Hsp90

Open access
Sato, Saori, Fujita, Naoya, Tsuruo, Takashi·2000·Proceedings of the National Academy of Sciences

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 Hsp90β 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.

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Metadata

Authors
Sato, S., Fujita, N., & Tsuruo, T.
Venue
Proceedings of the National Academy of Sciences
Published
2000-09-19
Volume
97
Issue
20
Pages
10832-10837
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2074579328
Cited by
967
References
1
FWCI
13.86
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Modulation of Akt kinase activity by binding to Hsp90. https://app.cochat.ai/papers/10.1073/pnas.170276797
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Sato, S., Fujita, N., & Tsuruo, T. (2000). Modulation of Akt kinase activity by binding to Hsp90. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.170276797

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