title: Internalization of fibroblast growth factor receptor is inhibited by a point mutation at tyrosine 766.
abstract: Binding of fibroblast growth factor (FGF) to the fibroblast growth factor receptor leads to autophosphorylation of the receptor on several tyrosine residues. Wild-type FGF receptor 1 (flg) and a mutated receptor (Y766F), in which an autophosphorylation site (Tyr-766) was mutated to phenylalanine, were expressed in rat myoblasts and in hematopoietic Ba/F3 cells. It was found that the point mutation at Tyr-766 resulted in a decrease in FGF receptor internalization, as well as a reduction in both ligand-induced FGF receptor down-regulation and degradation. It has been shown previously that phosphorylation of Tyr-766 is essential for interaction with phospholipase C gamma and that the Y766F FGF receptor mutant is unable to stimulate phosphatidylinositol hydrolysis and Ca2+ release from internal stores. The results presented in this report indicate that Tyr-766 is also essential for cellular trafficking of FGF receptor.
authors.affiliation: Department of Pharmacology, New York University Medical Center, New York 10016.
authors.forename: A
authors.initials: A
authors.lastname: Sorokin
authors.forename: M
authors.initials: M
authors.lastname: Mohammadi
authors.forename: J
authors.initials: J
authors.lastname: Huang
authors.forename: J
authors.initials: J
authors.lastname: Schlessinger
mesh_terms: D000818:Animals; D001483:Base Sequence; D015536:Down-Regulation / Q000187:drug effects; D004705:Endocytosis / Q000187:drug effects; D016220:Fibroblast Growth Factor 1 / Q000378:metabolism*; D006493:Heparin / Q000494:pharmacology; D007739:L Cells; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D019000:Phosphotyrosine; D017468:Receptors, Fibroblast Growth Factor / Q000737:chemistry / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D009838:Oligodeoxyribonucleotides; D017468:Receptors, Fibroblast Growth Factor; D016220:Fibroblast Growth Factor 1; D019000:Phosphotyrosine; D014443:Tyrosine; D006493:Heparin