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Demonstration of functionally different interactions between phospholipase C-gamma and the two types of platelet-derived growth factor receptors

Eriksson, Anders ; Nånberg, Eeva ; Rönnstrand, Lars LU orcid ; Engström, Ulla ; Hellman, Ulf ; Rupp, Eva ; Carpenter, Graham ; Heldin, Carl-Henrik and Claesson-Welsh, Lena (1995) In Journal of Biological Chemistry 270(13). p.7773-7781
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... (More)
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. (Less)
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publishing date
type
Contribution to journal
publication status
published
subject
keywords
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
in
Journal of Biological Chemistry
volume
270
issue
13
pages
7773 - 7781
publisher
American Society for Biochemistry and Molecular Biology
ISSN
1083-351X
language
English
LU publication?
no
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Experimental Clinical Chemistry (013016010)
id
734992bd-8e52-41c5-9de2-9262322bf9c3 (old id 1783970)
date added to LUP
2016-04-04 07:57:54
date last changed
2025-04-04 13:55:56
@article{734992bd-8e52-41c5-9de2-9262322bf9c3,
  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.}},
  author       = {{Eriksson, Anders and Nånberg, Eeva and Rönnstrand, Lars and Engström, Ulla and Hellman, Ulf and Rupp, Eva and Carpenter, Graham and Heldin, Carl-Henrik and Claesson-Welsh, Lena}},
  issn         = {{1083-351X}},
  keywords     = {{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}},
  language     = {{eng}},
  number       = {{13}},
  pages        = {{7773--7781}},
  publisher    = {{American Society for Biochemistry and Molecular Biology}},
  series       = {{Journal of Biological Chemistry}},
  title        = {{Demonstration of functionally different interactions between phospholipase C-gamma and the two types of platelet-derived growth factor receptors}},
  volume       = {{270}},
  year         = {{1995}},
}