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Hsp90 restrains ErbB‐2/HER2 signalling by limiting heterodimer formation
Author(s) -
Citri Ami,
Gan Judith,
Mosesson Yaron,
Vereb Gyorgi,
Szollosi Janos,
Yarden Yosef
Publication year - 2004
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/sj.embor.7400300
Subject(s) - erbb , hsp90 , microbiology and biotechnology , receptor tyrosine kinase , signal transduction , phosphorylation , receptor , biology , tyrosine kinase , chemistry , biochemistry , gene , heat shock protein
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.