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

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Author

  • Lars Rönnstrand
  • Seijiro Mori
  • Ann-Kristin Arvidsson
  • Anders Eriksson
  • Christer Wernstedt
  • Ulf Hellman
  • Lena Claesson-Welsh
  • Carl-Henrik Heldin

Summary, in English

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.

Publishing year

1992

Language

English

Pages

3911-3919

Publication/Series

EMBO Journal

Volume

11

Issue

11

Document type

Journal article

Publisher

Oxford University Press

Topic

  • Medicinal Chemistry

Keywords

  • 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

Status

Published

ISBN/ISSN/Other

  • ISSN: 1460-2075