Ligand-responsive EGFR mutants Binding of ligand-responsive EGFR mutants to chaperoning proteins HSP90 and CDC37 Authored: Orlic-Milacic, M, 2011-11-04 EGFR kinase domain mutants need continuous association with HSP90 chaperone protein for proper functioning. CDC37 is a co-chaperone of HSP90 that acts as a scaffold and regulator of interaction between HSP90 and its protein kinase clients. CDC37 binds a protein kinase through its N-terminal domain and HSP90 through its C-terminal domain, arresting ATP-ase activity of HSP90 and enabling the loading of a client kinase. CDC37 is frequently over-expressed in cancers involving mutant kinases and acts as an oncogene (reviewed by Gray Jr. et al. 2008). Association of EGFR extracellular domain point mutants with HSP90 chaperone has not been tested. Edited: D'Eustachio, P, 2011-11-07 Edited: Matthews, L, 2011-11-07 Edited: Wu, G, 2011-11-07 Pubmed14718169 Pubmed16024644 Pubmed16849543 Reactome Database ID Release 431218833 Reactome, http://www.reactome.org ReactomeREACT_115768 Reviewed: Greulich, H, 2011-11-15 Reviewed: Savas, S, 2011-11-15 has a Stoichiometric coefficient of 2 Ligand-responsive EGFR mutants:HSP90:CDC37 CDC37 HSP90