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.


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 Grb14 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 Grb14. Only the pY766 phosphopeptide mimetic of the PLCgamma binding site on FGFR released the inhibitory action of Grb14.


CONCLUSIONS
Grb14 binds to the Y766 site of MDA-MB-231-FGFR, competing for PLCy activation, thus inducing an arrest of the signaling transduction cascades.
Cailliau
Katia
K
Université des Sciences et Technologies de Lille, Laboratoire de Biologie du Développement, UE 1033, IFR 118, Bâtiment SN3, 59 655 Villeneuve d'Ascq, France.
Perdereau
Dominique
D
Lescuyer
Arlette
A
Chen
Huixiong
H
Garbay
Christiane
C
Vilain
Jean Pierre
JP
Burnol
Anne-Françoise
AF
Browaeys-Poly
Edith
E
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology; D006801:Humans; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D019000:Phosphotyrosine / Q000378:metabolism; D011506:Proteins / Q000378:metabolism / Q000494:pharmacology*; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014161:Transduction, Genetic; D014982:Xenopus laevis
D048868:Adaptor Proteins, Signal Transducing; C099655:GRB14 protein, human; D010446:Peptide Fragments; D011506:Proteins; D016220:Fibroblast Growth Factor 1; D019000:Phosphotyrosine; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051058:Oncogene Protein v-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D048055:Mitogen-Activated Protein Kinase 8