Hsp90 restrains ErbB-2/HER2 signalling by limiting heterodimer formation

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Updated: Aug 20, 2026

Studies of Chaperone-Cochaperone Interactions using Homogenous Bead-Based Assay
06:51

Studies of Chaperone-Cochaperone Interactions using Homogenous Bead-Based Assay

Published on: July 21, 2021

Ami Citri1, Judith Gan, Yaron Mosesson

  • 1Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.

EMBO Reports
|November 30, 2004
PubMed

Insights

Heat shock protein 90 (Hsp90) acts as a molecular switch, controlling the ErbB signalling network. Hsp90 limits ErbB-2 receptor complex formation and kinase activity, extending its role beyond protein stability.

Area of Science:

  • Molecular Biology
  • Cell Signalling
  • Oncology

Background:

  • ErbB-2/HER2 is an oncogenic tyrosine kinase crucial for cell signalling.
  • Heat shock protein 90 (Hsp90) and co-chaperones regulate ErbB-2 protein degradation.
  • The precise role of Hsp90 in modulating the broader ErbB signalling network is not fully understood.

Purpose of the Study:

  • To investigate the role of Hsp90 in regulating the ErbB signalling network beyond protein stability.
  • To elucidate the mechanism by which Hsp90 modulates ErbB-2 function and heterodimerization.

Main Methods:

  • Investigated the interaction between Hsp90 and ErbB-2.
  • Assessed the effect of Hsp90 on ligand-induced heterodimerization of ErbB receptors.
  • Characterized the binding site of Hsp90 on the ErbB-2 kinase domain.

Main Results:

  • Hsp90 limits the capacity of ErbB-2 to recruit ligand-bound receptors into active heterodimers.
  • Hsp90 dissociates from ErbB-2 upon ligand-induced heterodimerization.
  • Hsp90 binds a specific loop in the ErbB-2 kinase domain, restraining its catalytic function.

Conclusions:

  • Hsp90 acts as a molecular switch regulating the ErbB signalling network.
  • Hsp90's function extends to limiting the formation of ErbB-2-centered receptor complexes.
  • This regulation is critical for controlling ErbB-2 signalling output.

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