Grb14 inhibits FGF receptor signaling through the regulation of PLCγ recruitment and activation.
To decipher the mechanism involved in Grb14 binding to the activated fibroblast growth factor receptor (FGFR), we used the bioluminescence resonance energy transfer (BRET) technique and the Xenopus oocyte model. We showed that Grb14 was recruited to FGFR1 into a trimeric complex containing also phospholipase C gamma (PLCγ). The presence ... of Grb14 altered FGF-induced PLCγ phosphorylation and activation. Grb14-FGFR interaction involved the Grb14-SH2 domain and the FGFR pY766 residue, which is the PLCγ binding site. Our data led to a molecular model whereby Grb14 binding to the phosphorylated FGFR induces a conformational change that unmasks a PLCγ binding motif on Grb14, allowing trapping and inactivation of PLCγ.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Animals, Cell Line, Cell Survival, Energy Transfer, Enzyme Activation, Fibroblast Growth Factors, Humans, Oocytes, Phospholipase C gamma, Receptor, Fibroblast Growth Factor, Type 1, Signal Transduction, Xenopus
Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Animals, Cell Line, Cell Survival, Energy Transfer, Enzyme Activation, Fibroblast Growth Factors, Humans, Oocytes, Phospholipase C gamma, Receptor, Fibroblast Growth Factor, Type 1, Signal Transduction, Xenopus
FEBS Lett.
Date: Nov. 05, 2010
PubMed ID: 20932831
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