Demonstration of functionally different interactions between phospholipase C-gamma and the two types of platelet-derived growth factor receptors.
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.
Mesh Terms:
Amino Acid Sequence, Animals, Aorta, Base Sequence, Binding, Competitive, Cell Division, Endothelium, Vascular, Isoenzymes, Kinetics, Molecular Sequence Data, Mutagenesis, Site-Directed, Oligodeoxyribonucleotides, Peptide Fragments, Phospholipases, Phosphopeptides, Phosphorylation, Phosphotyrosine, Platelet-Derived Growth Factor, Point Mutation, Receptor Protein-Tyrosine Kinases, Receptor, Platelet-Derived Growth Factor alpha, Receptor, Platelet-Derived Growth Factor beta, Receptors, Platelet-Derived Growth Factor, Recombinant Proteins, Sequence Homology, Amino Acid, Swine, Thymidine, Tyrosine
Amino Acid Sequence, Animals, Aorta, Base Sequence, Binding, Competitive, Cell Division, Endothelium, Vascular, Isoenzymes, Kinetics, Molecular Sequence Data, Mutagenesis, Site-Directed, Oligodeoxyribonucleotides, Peptide Fragments, Phospholipases, Phosphopeptides, Phosphorylation, Phosphotyrosine, Platelet-Derived Growth Factor, Point Mutation, Receptor Protein-Tyrosine Kinases, Receptor, Platelet-Derived Growth Factor alpha, Receptor, Platelet-Derived Growth Factor beta, Receptors, Platelet-Derived Growth Factor, Recombinant Proteins, Sequence Homology, Amino Acid, Swine, Thymidine, Tyrosine
J. Biol. Chem.
Date: Mar. 31, 1995
PubMed ID: 7535778
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