PathwayStep4213 PathwayStep4216 PathwayStep4217 PathwayStep4214 PathwayStep4215 Constitutive dimerization of FGFR4 Y367C mutant Dimerization of FGFR4 mutants with enhanced kinase activity Autocatalytic phosphorylation of FGFR4 Y367C mutant Autocatalytic phosphorylation of FGFR4 mutants with enhanced kinase activity FGFR4 kinase mutants are inhibited by PD170734 Signaling by FGFR4 mutants Authored: Rothfels, K, 2012-02-09 Edited: Rothfels, K, 2012-05-16 FGFR4 is perhaps the least well studied of the FGF receptors, and unlike the case for the other FGFR genes, mutations in FGFR4 are not known to be associated with any developmental disorders. Recently, however, somatically arising mutations in the FGFR4 coding sequence have begun to be identified in some cancers. 8% of rhabdomyosarcomas have activating mutations in the kinase domain of FGFR4. Two of these mutations - N535K (paralogous to the FGFR2 N550K allele found in endometrial cancers) and V550E - have been shown to support the oncogenic transformation of NIH 3T3 cells (Taylor, 2009). An FGFR4 Y367C mutation has also been identified in breast cancers (Ruhe, 2007; Roidl, 2010); mutations of paralogous residues in FGFR2 and FGFR3 are associated with both skeletal dysplasias and the development of diverse cancers (Pollock, 2007; Ruhe, 2007; Rousseau, 1996; Chesi, 1997, 2001).<br><br><br>Finally, a SNP at position 388 of FGFR4 is associated with aggressive disease development. Expression of the G388R allele in breast, colorectal and prostate cancers is correlated with rapid progression times and increased rates of recurrence and metastasis (Bange, 2002; Spinola, 2005; Wang, 2004). Pubmed11157491 Pubmed11830541 Pubmed15448004 Pubmed16012724 Pubmed17525745 Pubmed18056464 Pubmed19809159 Pubmed19946327 Pubmed8845844 Pubmed9207791 Reactome Database ID Release 431839128 Reactome, http://www.reactome.org ReactomeREACT_121286 Reviewed: Ezzat, S, 2012-05-15