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Identification of two C-terminal autophosphorylation sites in the PDGF beta-receptor: involvement in the interaction with phospholipase C-gamma

Rönnstrand, Lars LU ; Mori, Seijiro; Arvidsson, Ann-Kristin; Eriksson, Anders; Wernstedt, Christer; Hellman, Ulf; Claesson-Welsh, Lena and Heldin, Carl-Henrik (1992) In EMBO Journal 11(11). p.3911-3919
Abstract
Two novel sites of autophosphorylation were localized to the C-terminal tail of the PDGF beta-receptor. To evaluate the importance of these phosphorylation sites, receptor mutants in which Tyr1009, Tyr1021 or both were replaced with phenylalanine residues, were expressed in porcine aortic endothelial (PAE) cells. These mutants were similar to the wild type receptor with regard to protein tyrosine kinase activity and ability to induce mitogenicity in response to PDGF-BB. However, both the Y1009F and Y1021F mutants showed a decreased ability to mediate association with and the tyrosine phosphorylation of phospholipase C-gamma (PLC-gamma) compared to the wild type PDGF beta-receptor; in the case of the Y1009F/Y1021F double mutant, no... (More)
Two novel sites of autophosphorylation were localized to the C-terminal tail of the PDGF beta-receptor. To evaluate the importance of these phosphorylation sites, receptor mutants in which Tyr1009, Tyr1021 or both were replaced with phenylalanine residues, were expressed in porcine aortic endothelial (PAE) cells. These mutants were similar to the wild type receptor with regard to protein tyrosine kinase activity and ability to induce mitogenicity in response to PDGF-BB. However, both the Y1009F and Y1021F mutants showed a decreased ability to mediate association with and the tyrosine phosphorylation of phospholipase C-gamma (PLC-gamma) compared to the wild type PDGF beta-receptor; in the case of the Y1009F/Y1021F double mutant, no association or phosphorylation of PLC-gamma could be detected. These data show that tyrosine phosphorylation of PLC-gamma is dependent on autophosphorylation of the PDGF beta-receptor at Tyr1009 and Tyr1021. (Less)
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@article{5eb4d691-1744-44aa-9c5f-264fb0935955,
  abstract     = {Two novel sites of autophosphorylation were localized to the C-terminal tail of the PDGF beta-receptor. To evaluate the importance of these phosphorylation sites, receptor mutants in which Tyr1009, Tyr1021 or both were replaced with phenylalanine residues, were expressed in porcine aortic endothelial (PAE) cells. These mutants were similar to the wild type receptor with regard to protein tyrosine kinase activity and ability to induce mitogenicity in response to PDGF-BB. However, both the Y1009F and Y1021F mutants showed a decreased ability to mediate association with and the tyrosine phosphorylation of phospholipase C-gamma (PLC-gamma) compared to the wild type PDGF beta-receptor; in the case of the Y1009F/Y1021F double mutant, no association or phosphorylation of PLC-gamma could be detected. These data show that tyrosine phosphorylation of PLC-gamma is dependent on autophosphorylation of the PDGF beta-receptor at Tyr1009 and Tyr1021.},
  author       = {Rönnstrand, Lars and Mori, Seijiro and Arvidsson, Ann-Kristin and Eriksson, Anders and Wernstedt, Christer and Hellman, Ulf and Claesson-Welsh, Lena and Heldin, Carl-Henrik},
  issn         = {1460-2075},
  keyword      = {Amino Acid Sequence
Animals
Base Sequence
Cell Line
Female
Isoenzymes/*metabolism
Kinetics
Macromolecular Substances
Models,Site-Directed
Oligodeoxyribonucleotides
Peptide Fragments/isolation & purification
Peptide Mapping
Phosphates/*metabolism
Phosphopeptides/isolation & purification
Phosphorylation
Plasmids
Platelet-Derived Growth Factor/*metabolism
Receptors,Structural
Molecular Sequence Data
Mutagenesis,Platelet-Derived Growth Factor/genetics/*metabolism
Recombinant Proteins/metabolism
Swine
Transfection
Type C Phospholipases/*metabolism
Uterus/metabolism},
  language     = {eng},
  number       = {11},
  pages        = {3911--3919},
  publisher    = {Oxford University Press},
  series       = {EMBO Journal},
  title        = {Identification of two C-terminal autophosphorylation sites in the PDGF beta-receptor: involvement in the interaction with phospholipase C-gamma},
  volume       = {11},
  year         = {1992},
}