Hsp90-dependent activation of protein kinases is regulated by chaperone-targeted dephosphorylation of Cdc37

Vaughan, Cara K., Mollapour, Mehdi, Smith, Jennifer R., Truman, Andrew W., Hu, Bin, Good, Valerie M., Panaretou, Barry, Neckers, Len, Clarke, Paul A., Workman, Paul, and others. (2008) Hsp90-dependent activation of protein kinases is regulated by chaperone-targeted dephosphorylation of Cdc37. Molecular Cell, 31 (6). pp. 886-895. ISSN 1097-2765. (doi:10.1016/j.molcel.2008.07.021) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided) (KAR id:40380)

The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided.
Official URL: http://dx.doi.org/10.1016/j.molcel.2008.07.021

Abstract

Activation of protein kinase clients by the Hsp90 system is mediated by the cochaperone protein Cdc37. Cdc37 requires phosphorylation at Ser13, but little is known about the regulation of this essential posttranslational modification. We show that Ser13 of uncomplexed Cdc37 is phosphorylated in vivo, as well as in binary complex with a kinase (C-K), or in ternary complex with Hsp90 and kinase (H-C-K). Whereas pSer13-Cdc37 in the H-C-K complex is resistant to nonspecific phosphatases, it is efficiently dephosphorylated by the chaperone-targeted protein phosphatase 5 (PP5/Ppt1), which does not affect isolated Cdc37. We show that Cdc37 and PP5/Ppt1 associate in Hsp90 complexes in yeast and in human tumor cells, and that PP5/Ppt1 regulates phosphorylation of Ser13-Cdc37 in vivo, directly affecting activation of protein kinase clients by Hsp90-Cdc37. These data reveal a cyclic regulatory mechanism for Cdc37, in which its constitutive phosphorylation is reversed by targeted dephosphorylation in Hsp90 complexes.

Item Type:	Article
DOI/Identification number:	10.1016/j.molcel.2008.07.021
Additional information:	Mollapour designated joint first author; number of additional authors: 12;
Subjects:	Q Science
Divisions:	Divisions > Division of Natural Sciences > Biosciences
Depositing User:	Stewart Brownrigg
Date Deposited:	07 Mar 2014 00:05 UTC
Last Modified:	05 Nov 2024 10:24 UTC
Resource URI:	https://kar.kent.ac.uk/id/eprint/40380 (The current URI for this page, for reference purposes)

University of Kent Author Information

Mollapour, Mehdi.

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