Binding of ligand-responsive EGFR mutants to chaperoning proteins HSP90 and CDC37

Stable Identifier
R-HSA-1218833
Type
Reaction [transition]
Species
Homo sapiens
Compartment
plasma membrane, cytosol
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Binding of ligand-responsive EGFR mutants to chaperoning proteins HSP90 and CDC37
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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.

Literature References
PubMed ID Title Journal Year
16024644 Epidermal growth factor receptors harboring kinase domain mutations associate with the heat shock protein 90 chaperone and are destabilized following exposure to geldanamycins

Shimamura, T, Lowell, AM, Engelman, JA, Shapiro, GI

Cancer Res 2005
14718169 The Mechanism of Hsp90 regulation by the protein kinase-specific cochaperone p50(cdc37)

Roe, SM, Ali, MM, Meyer, P, Vaughan, CK, Panaretou, B, Piper, PW, Prodromou, C, Pearl, LH

Cell 2004
16849543 Association with HSP90 inhibits Cbl-mediated down-regulation of mutant epidermal growth factor receptors

Yang, S, Qu, S, Perez-Tores, M, Sawai, A, Rosen, N, Solit, DB, Arteaga, CL

Cancer Res 2006
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Functional status

Gain of function of Ligand-responsive EGFR mutants [plasma membrane]

Disease Entity
Status
Disease
Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
Authored
Orlic-Milacic, M  (2011-11-04)
Reviewed
Greulich, H  (2011-11-15)
Savas, S  (2011-11-15)
Created
Orlic-Milacic, M  (2011-02-18)
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