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Modulation of Akt kinase activity by binding to Hsp90
Open accessAbstract
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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Borkovich, K. A., Farrelly, F. W., Finkelstein, D. B., Taulien, J., & Lindquist, S. (1989) · Molecular and Cellular Biology · doi:10.1128/mcb.9.9.3919 · Cited by 641
Cited by
Hayden, M. S., & Ghosh, S. (2004) · Genes & Development · doi:10.1101/gad.1228704 · Cited by 3,842
Missing Pieces in the NF-κB Puzzle
Ghosh, S., & Karin, M. (2002) · Cell · doi:10.1016/s0092-8674(02)00703-1 · Cited by 3,638
HSP90 at the hub of protein homeostasis: emerging mechanistic insights
Taipale, M., Jarosz, D. F., & Lindquist, S. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2918 · Cited by 1,818
Hayden, M. S., West, A. P., & Ghosh, S. (2006) · Oncogene · doi:10.1038/sj.onc.1209943 · Cited by 1,178
Apoptosis and Molecular Targeting Therapy in Cancer
Hassan, M., Watari, H., AbuAlmaaty, A., Ohba, Y., & Sakuragi, N. (2014) · BioMed Research International · doi:10.1155/2014/150845 · Cited by 1,121
Retracted
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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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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