title: Demonstration of functionally different interactions between phospholipase C-gamma and the two types of platelet-derived growth factor receptors.
abstract: Phosphorylated tyrosine residues in receptor tyrosine kinases serve as binding sites for signal transduction molecules. We have identified two autophosphorylation sites, Tyr-988 and Tyr-1018, in the platelet-derived growth factor (PDGF) alpha-receptor carboxyl-terminal tail, which are involved in binding of phospholipase C-gamma (PLC-gamma). The capacities of the Y988F and Y1018F mutant PDGF alpha-receptors, expressed in porcine aortic endothelial cells, to bind PLC-gamma are 60 and 5% of that of the wild-type receptor, respectively. Phosphorylated but not unphosphorylated peptides containing Tyr-1018 are able to compete with the intact receptor for binding to immobilized PLC-gamma SH2 domains; a phosphorylated Tyr-988 peptide competes 10 times less efficiently. The complex between PLC-gamma and the PDGF alpha-receptor is more stable than that of PLC-gamma and the PDGF beta-receptor. However, PDGF stimulation results in a smaller fraction of tyrosine-phosphorylated PLC-gamma and a smaller accumulation of inositol trisphosphate in cells expressing the alpha-receptor as compared with cells expressing the beta-receptor. We conclude that phosphorylated Tyr-988 and Tyr-1018 in the PDGF alpha-receptor carboxyl-terminal tail bind PLC-gamma, but this association leads to only a relatively low level of tyrosine phosphorylation and activation of PLC-gamma.
authors.affiliation: Ludwig Institute for Cancer Research, Uppsala, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Eriksson
authors.forename: E
authors.initials: E
authors.lastname: Nånberg
authors.forename: L
authors.initials: L
authors.lastname: Rönnstrand
authors.forename: U
authors.initials: U
authors.lastname: Engström
authors.forename: U
authors.initials: U
authors.lastname: Hellman
authors.forename: E
authors.initials: E
authors.lastname: Rupp
authors.forename: G
authors.initials: G
authors.lastname: Carpenter
authors.forename: C H
authors.initials: CH
authors.lastname: Heldin
authors.forename: L
authors.initials: L
authors.lastname: Claesson-Welsh
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001011:Aorta; D001483:Base Sequence; D000077214:Becaplermin; D001667:Binding, Competitive; D002455:Cell Division; D004730:Endothelium, Vascular / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism*; D007700:Kinetics; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009838:Oligodeoxyribonucleotides; D010446:Peptide Fragments / Q000737:chemistry / Q000302:isolation & purification; D010740:Phospholipases / Q000378:metabolism*; D010748:Phosphopeptides / Q000494:pharmacology; D010766:Phosphorylation; D019000:Phosphotyrosine; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D017354:Point Mutation; D020574:Proto-Oncogene Proteins c-sis; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid; D013552:Swine; D013936:Thymidine / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D007527:Isoenzymes; D009838:Oligodeoxyribonucleotides; D010446:Peptide Fragments; D010748:Phosphopeptides; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D011994:Recombinant Proteins; D000077214:Becaplermin; D019000:Phosphotyrosine; D014443:Tyrosine; D020794:Receptor Protein-Tyrosine Kinases; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor; D010740:Phospholipases; D013936:Thymidine