Activated FGFR1 binds PLCG1

Recruitment of PLC-gamma by FGF receptors has been best studied in FGFR1c signaling, where it has been shown that autophosphorylation of Tyr766 in the C-terminal tail of FGFR1c creates a specific binding site for the SH2 domain of PLC-gamma. A mutant FGFR1c in which Y766 is replaced by phenylalanine is unable to activate PI hydrolysis and Ca2+ release in response to FGF stimulation. Membrane recruitment of PLC-gamma is also aided by binding of the Pleckstrin homology (PH) domain of this enzyme to PtIns(3,4,5) P3 molecules that are generated in response to PI-3 kinase stimulation. By sequence comparison, Y766 is conserved in all FGFR isoforms, and PLC-gamma signaling is observed, to a greater or lesser extent, downstream of all FGFR receptors upon stimulation with FGFs.

PLC-γ受体由FGF受体招募的研究主要集中于FGFR1c信号通路，研究表明，FGFR1c的C端尾部的Tyr766残基的自身磷酸化形成了一个PLC-γSH2结构域的特异性结合位点。在FGFR1c中，将Y766替换为苯丙氨酸的突变体无法在FGF刺激下激活PI的水解和Ca2+的释放。PLC-γ的膜招募还受到该酶的Pleckstrin同源（PH）结构域与PI-3激酶刺激产生的PtIns(3,4,5)P3分子的结合所促进。序列比较显示，Y766在所有FGFR同源体中均得到保守，且在FGFs刺激下，PLC-γ信号通路在所有FGFR受体下游均有所观察，程度有所不同。