Hsp90 Restrains ErbB-2/HER2 Signalling by Limiting Heterodimer Formation

Overview

Journal EMBO Rep

Specialty Molecular Biology

Date 2004 Nov 30

PMID 15568014

Citations 68

Authors

Ami Citri

Judith Gan

Yaron Mosesson

Gyorgi Vereb

Janos Szollosi

Yosef Yarden

Affiliations

Soon will be listed here.

Abstract

ErbB-2/HER2 is an oncogenic tyrosine kinase that regulates a signalling network by forming ligand-induced heterodimers with several growth factor receptors of the ErbB family. Hsp90 and co-chaperones regulate degradation of ErbB-2 but not other ErbB members. Here, we report that the role of Hsp90 in modulating the ErbB network extends beyond regulation of protein stability. The capacity of ErbB-2 to recruit ligand-bound receptors into active heterodimers is limited by Hsp90, which is dissociated from ErbB-2 following ligand-induced heterodimerization. We show that Hsp90 binds a specific loop within the kinase domain of ErbB-2, thereby restraining heterodimer formation and catalytic function. These results define a role for Hsp90 as a molecular switch regulating the ErbB signalling network by limiting formation of ErbB-2-centred receptor complexes.

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