title: FGF receptor phosphotyrosine 766 is a target for Grb14 to inhibit MDA-MB-231 human breast cancer cell signaling.
abstract: 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.
authors.affiliation: Université des Sciences et Technologies de Lille, Laboratoire de Biologie du Développement, UE 1033, IFR 118, Bâtiment SN3, 59 655 Villeneuve d'Ascq, France.
authors.forename: Katia
authors.initials: K
authors.lastname: Cailliau
authors.forename: Dominique
authors.initials: D
authors.lastname: Perdereau
authors.forename: Arlette
authors.initials: A
authors.lastname: Lescuyer
authors.forename: Huixiong
authors.initials: H
authors.lastname: Chen
authors.forename: Christiane
authors.initials: C
authors.lastname: Garbay
authors.forename: Jean Pierre
authors.initials: JP
authors.lastname: Vilain
authors.forename: Anne-Françoise
authors.initials: AF
authors.lastname: Burnol
authors.forename: Edith
authors.initials: E
authors.lastname: Browaeys-Poly
mesh_terms: 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
chemical_list: 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