PathwayStep4197 PathwayStep4198 PathwayStep4195 PathwayStep4196 Autocatalytic phosphorylation of overexpressed FGFR2 variants Tyrosine kinase inhibitors bind to overexpressed FGFR2 variants Dimerization of overexpressed FGFR2 GP369 inhibits activation of amplified FGFR2 signaling Signaling by FGFR2 amplification mutants Authored: Rothfels, K, 2012-02-09 Edited: Rothfels, K, 2012-05-16 FGFR2 amplifications have been identified in 10% of gastric cancers, where they are associated with poor prognosis diffuse cancers (Hattori, 1996; Ueda, 1999; Shin, 2000; Kunii, 2008) , and in ~1% of breast cancers (Turner, 2010; Tannheimer, 2000). FGFR2 amplification often occur in conjunction with deletions of C-terminal exons, resulting in expression of a internalization- and degradation-resistant form of the receptor (Takeda, 1999; Cha, 2008, 2009). Amplification affects signaling without altering the intrinsic kinase activity of the receptor. Signaling through overexpressed FGFR2 also shows evidence of being ligand-independent and sensitive to FGFR inhibitors (Lorenzi, 1997; Takeda, 1999; Cha, 2009). Pubmed10626794 Pubmed11003564 Pubmed11056689 Pubmed17505008 Pubmed18337450 Pubmed18381441 Pubmed19103595 Pubmed20101236 Pubmed9266968 Pubmed9816310 Reactome Database ID Release 432023837 Reactome, http://www.reactome.org ReactomeREACT_121255 Reviewed: Ezzat, S, 2012-05-15