FGFR4 enhanced kinase mutants Dimerization of FGFR4 mutants with enhanced kinase activity Authored: Rothfels, K, 2012-02-09 Edited: Rothfels, K, 2012-05-16 FGFR4 is highly expressed in rhabdomyosarcoma (RMS) tissue, and high levels of expression are correlated with lower survival. Sequencing of exons from 94 RMS tumors identified 14 missense variants, 6 of which were localized in the tyrosine kinase domain, and four of which were in two amino acids (N535K/D and V550E/L). Mutations at amino acid 535 are predicted to eliminate an inhibitory H-bond that restricts receptor autophosphorylation, and mutations at amino acid 550 are believed to alter the ATP-binding site. Functional studies on N535K and V550 show that they undergo autophosphorylation when transfected into a murine RMS lines and transformed NIH 3T3 cells, leading to a metastatic phenotype (Taylor, 2009). Pubmed19809159 Reactome Database ID Release 432038946 Reactome, http://www.reactome.org ReactomeREACT_121020 Reviewed: Ezzat, S, 2012-05-15 has a Stoichiometric coefficient of 2 FGFR4 enhanced kinase mutant dimers