Display Settings:

Format

Send to:

Choose Destination
We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Oncogene. 1996 Mar 21;12(6):1213-22.

A role for activated p21 ras in inhibition/regulation of platelet-derived growth factor (PDGF) type-beta receptor activation.

Author information

  • 1Cancer Research Center, Boston University School of Medicine, MA 02118, USA.

Abstract

Ligand-stimulated Platelet-Derived Growth Factor (PDGF) type-beta receptor autophosphorylation, and tyrosine phosphorylation of receptor-associated signalling proteins, is blocked in cells expressing activated Ras genes. A factor present in membrane fractions of v-ras-expressing fibroblasts (Kbalb cells) dominantly inhibits the autophosphorylation of the PDGF type-beta receptor. Purification of this factor, via ion exchange, reveals that the inhibitor can be physically separated from the PDGF type-beta receptor, with reconstitution of PDGF type-beta receptor kinase activity in response to ligand binding. The inhibitor exhibited specificity for the PDGF type-beta receptor, and consistently co-purified with activated p21 ras, with Syp/PTP-2, and with Grb2. Neutralization of the p21 ras protein from the Kbalb cell membranes by p21 ras-specific monoclonal antibodies, however, completely removed the inhibition of PDGF type-beta receptor, rendering the PDGF type-beta receptor molecule capable of autophosphorylation in response to ligand. These results indicate that activated p21 ras either interacts directly with the PDGF type-beta receptor to inhibit autokinase activity, or complexes with different molecules such as Syp and/or Grb2 at the cell membrane to act on another effector which then inhibits PDGF type-beta receptor function.

PMID:
8649823
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Loading ...
    Write to the Help Desk