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Increased mitogenicity of an alphabeta heterodimeric PDGF receptor complex correlates with lack of RasGAP binding

In English

Författare

Summary, in English

The different platelet-derived growth factor (PDGF) isoforms cause activation of their alpha and beta protein tyrosine kinase receptors through dimerization. Homodimerization as well as heterodimerization of receptors occur. It has been shown previously that the heterodimeric receptor complex mediates a stronger mitogenic response than either of the homodimeric complexes. In this report, we show that in cells expressing both PDGF alpha- and beta-receptors, stimulation with PDGF-AB, which leads to preferential heterodimer formation, leads to a very low degree of phosphorylation of Tyr771 in the beta-receptor. In contrast, Tyr771 is phosphorylated in a homodimeric complex of beta-receptors. Phosphorylated Tyr771 is a binding site for RasGAP; an analogous site is not present in the alpha-receptor, which lacks the ability to associate with RasGAP. The lowered phosphorylation of Tyr771 in the heterodimeric receptor complex correlates with lowered association with RasGAP, as well as with a more efficient activation of Ras and MAP kinase, which is consistent with the increased mitogenicity elicited by PDGF-AB, compared to PDGF-AA or PDGF-BB.

Publiceringsår

1999

Språk

Engelska

Sidor

2481-2488

Publikation/Tidskrift/Serie

Oncogene

Volym

18

Issue

15

Dokumenttyp

Artikel i tidskrift

Förlag

Nature Publishing Group

Ämne

  • Medicinal Chemistry

Nyckelord

  • Platelet-Derived Growth Factor alpha Receptor
  • Platelet-Derived Growth Factor beta Receptors
  • ras Mitogens/metabolism Molecular Sequence Data Mutation Phosphorylation Platelet-Derived Growth Factor/metabolism/pharmacology Protein Isoforms Proteins/*metabolism Receptor
  • Amino Acid Sequence Animals Binding Sites Calcium-Calmodulin-Dependent Protein Kinases/drug effects/metabolism Cell Line Dimerization Endothelium
  • Vascular/cytology/drug effects/metabolism Enzyme Activation GTPase-Activating Proteins Genes
  • Platelet-Derived Growth Factor/chemistry/genetics/*metabolism Swine Tyrosine/metabolism ras GTPase-Activating Proteins

Status

Published

ISBN/ISSN/Övrigt

  • ISSN: 1476-5594