FGF Receptor Phosphotyrosine 766 is a Target for Grb14 to Inhibit MDA-MB-231 Human Breast Cancer Cell Signaling

Background: Fibroblast growth factors receptors (FGFRs) are involved in estrogen-independent breast cancer cell growth. Grbl4, a member of the Grb7 family of adapters, is an inhibitor of FGFR signaling. Materials and Methods: FGFR from highly invasive MDA-MB-231 cells were expressed in Xenopus oocyte, a widely used model system to question cascade transduction regulations. The effect of microinjection of Grbl4 and various mimetic peptides for FGFR tyrosine residues were analysed by FGFR immunoprecipitation and Western blot analysis of signaling cascades. Results: PLCy, ERK2, JNK1 and AKT were blocked by Grbl4. Only the pY766 phosphopeptide mimetic of the PLCy binding site on FGFR released the inhibitory action of Grbl4. Conclusion. Grbl4 binds to the Y766 site of MDA-MB-231-FGFR, competing for PLCy activation, thus inducing an arrest of the signaling transduction cascades.