Meta-Biol

• Pathways

The intrinsic protein tyrosine kinase activity of activated FGF receptor 3 catalyzes multiple phosphorylation events, creating a number of binding sites on its cytoplasmic tail for membrane bound docking proteins to gather intracellular signaling mediators. Based on sequence alignment, FGFR3 contains 6 of the 8 cytoplasmic tyrosine residues identified in FGFR1. Mutagenesis studies highlight the importance of tyrosine residue 724 in signaling mediated by FGFR3, including transformation, PPTN11/SHP2 phosphorylation, and activation of MAPK, PI3K and STAT pathways. These studies also identified a role for the PLCG1-binding tyrosine residue, Y760, in STAT activation, and a potential role for tyrosine 770 as a negative regulator of FGFR3 signaling.