Demonstration of functionally different interactions between phospholipase C-gamma and the two types of platelet-derived growth factor receptors
Författare
Summary, in English
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.
Publiceringsår
1995
Språk
Engelska
Sidor
7773-7781
Publikation/Tidskrift/Serie
Journal of Biological Chemistry
Volym
270
Issue
13
Dokumenttyp
Artikel i tidskrift
Förlag
American Society for Biochemistry and Molecular Biology
Ämne
- Medicinal Chemistry
Nyckelord
- Platelet-Derived Growth Factor/*metabolism Recombinant Proteins/pharmacology Sequence Homology
- Platelet-Derived Growth Factor alpha Receptor
- Platelet-Derived Growth Factor beta Receptors
- Site-Directed Oligodeoxyribonucleotides Peptide Fragments/chemistry/isolation & purification Phospholipases/*metabolism Phosphopeptides/pharmacology Phosphorylation Phosphotyrosine Platelet-Derived Growth Factor/pharmacology Point Mutation Receptor Protein-Tyrosine Kinases/metabolism Receptor
- Vascular/*metabolism Isoenzymes/*metabolism Kinetics Molecular Sequence Data Mutagenesis
- Amino Acid Sequence Animals Aorta Base Sequence Binding
- Competitive Cell Division Endothelium
- Amino Acid Swine Thymidine/metabolism Tyrosine/analogs & derivatives/metabolism
Status
Published
ISBN/ISSN/Övrigt
- ISSN: 1083-351X