Demonstration of functionally different interactions between phospholipase C-gamma and the two types of platelet-derived growth factor receptors
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1783970
- author
- Eriksson, Anders ; Nånberg, Eeva ; Rönnstrand, Lars LU ; Engström, Ulla ; Hellman, Ulf ; Rupp, Eva ; Carpenter, Graham ; Heldin, Carl-Henrik and Claesson-Welsh, Lena
- publishing date
- 1995
- 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
- 2019-05-22 02:18:23
@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}}, }