PathwayStep4179 PathwayStep4178 PathwayStep4181 PathwayStep4180 Dimerization of FGFR1 point mutants with enhanced kinase activity Autocatalytic phosphorylation of FGFR1 mutants with enhanced kinase activity FGFR1 P252X mutants bind ligand with enhanced affinity Autocatalytic phosphorylation of FGFR1 P252X mutant dimers Signaling by activated point mutants of FGFR1 Authored: Rothfels, K, 2012-02-09 Edited: Rothfels, K, 2012-05-16 Pubmed10053006 Pubmed11055896 Pubmed16140923 Pubmed16186508 Pubmed17552943 Pubmed18056464 Pubmed18772890 Pubmed20094046 Pubmed21711248 Pubmed7670477 Pubmed7773297 Pubmed7874169 Pubmed9154000 Pubmed9538690 Reactome Database ID Release 431839122 Reactome, http://www.reactome.org ReactomeREACT_121153 Reviewed: Ezzat, S, 2012-05-15 Unlike other FGFR2 and 3, FGFR1 appears not to be a frequent target of activating point mutations (reviewed in Wesche, 2011; Turner and Grose, 2010). Germline point mutations at residue P252 have been identified in Pfeiffer syndrome (reviewed in Webster and Donoghue, 1997; Burke, 1998; Cunningham, 2007) while mutation of the same residue arising somatically has been identified in melanoma and lung cancer (Ruhe, 2007; Davies, 2005). Two kinase domain mutations have been characterized in glioblastoma (Rand, 2005; Network TCGA, 2008), both at positions that are also mutated in an autosomal disorder in one of the FGFR family members (Muenke, 1994; Bellus, 1995a; Bellus, 2000; Tavormina, 1995a; Tavormina, 1999).