Activated point mutants in the transmembrane and kinase domains of FGFR3 have been shown to undergo constitutive autophosphorylation in a ligand-independent manner (Naski, 1996; Webster, 1996 and Donoghue, 1996; Webster, 1996; Bellus, 2000; Goriely, 2009). Some of the point mutants, including K650E and G380R, may also be able to further respond after exposure to ligand (Naski, 1996). Dimerization and activation of the FGFR3 transmembrane mutants is thought to occur via the formation of non-native hydrogen bonds that promote intermolecular interactions (Webster and Donoghue 1996), while the kinase domain mutants activate phosphorylation by mimicking conformational changes in the activation loop (Webster, 1996). Mutants with enhanced kinase activity appear to be activated to differing extents that, for the most part, correlate with the severity of the disease phenotype (Webster, 1996; Bellus, 2000; Goriely, 2009), although the results of in vitro kinase assays with immunoprecipitated proteins do not fully recapitulate the pathological consequences of the mutation (Goriely, 2009). K650E has also been shown to transform NIH 3T3 cells (Chesi, 2001).