Phosphorylation induced cochaperone unfolding promotes kinase recruitment and client class-specific Hsp90 phosphorylation.

Autor:	Bachman AB; Department of Chemistry, University of South Florida, Tampa, FL, 33620, USA., Keramisanou D; Department of Chemistry, University of South Florida, Tampa, FL, 33620, USA., Xu W; Urologic Oncology Branch, National Cancer Institute, Bethesda, MD, 20892, USA., Beebe K; Urologic Oncology Branch, National Cancer Institute, Bethesda, MD, 20892, USA., Moses MA; Urologic Oncology Branch, National Cancer Institute, Bethesda, MD, 20892, USA., Vasantha Kumar MV; Department of Chemistry, University of South Florida, Tampa, FL, 33620, USA., Gray G; Department of Chemistry, University of South Florida, Tampa, FL, 33620, USA., Noor RE; Department of Chemistry, University of South Florida, Tampa, FL, 33620, USA., van der Vaart A; Department of Chemistry, University of South Florida, Tampa, FL, 33620, USA., Neckers L; Urologic Oncology Branch, National Cancer Institute, Bethesda, MD, 20892, USA., Gelis I; Department of Chemistry, University of South Florida, Tampa, FL, 33620, USA. igelis@usf.edu.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2018 Jan 17; Vol. 9 (1), pp. 265. Date of Electronic Publication: 2018 Jan 17.
DOI:	10.1038/s41467-017-02711-w
Abstrakt:	During the Hsp90-mediated chaperoning of protein kinases, the core components of the machinery, Hsp90 and the cochaperone Cdc37, recycle between different phosphorylation states that regulate progression of the chaperone cycle. We show that Cdc37 phosphorylation at Y298 results in partial unfolding of the C-terminal domain and the population of folding intermediates. Unfolding facilitates Hsp90 phosphorylation at Y197 by unmasking a phosphopeptide sequence, which serves as a docking site to recruit non-receptor tyrosine kinases to the chaperone complex via their SH2 domains. In turn, Hsp90 phosphorylation at Y197 specifically regulates its interaction with Cdc37 and thus affects the chaperoning of only protein kinase clients. In summary, we find that by providing client class specificity, Hsp90 cochaperones such as Cdc37 do not merely assist in client recruitment but also shape the post-translational modification landscape of Hsp90 in a client class-specific manner.
Databáze:	MEDLINE
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