The small GTP-binding protein R-Ras can influence integrin activation by antagonizing a Ras/Raf-initiated integrin suppression pathway

Mol Biol Cell. 1999 Jun;10(6):1799-809. doi: 10.1091/mbc.10.6.1799.

Abstract

The rapid modulation of ligand-binding affinity ("activation") is a central property of the integrin family of cell adhesion receptors. The small GTP-binding protein Ras and its downstream effector kinase Raf-1 suppress integrin activation. In this study we explored the relationship between Ras and the closely related small GTP-binding protein R-Ras in modulating the integrin affinity state. We found that R-Ras does not seem to be a direct activator of integrins in Chinese hamster ovary cells. However, we observed that GTP-bound R-Ras strongly antagonizes the Ras/Raf-initiated integrin suppression pathway. Furthermore, this reversal of the Ras/Raf suppressor pathway does not seem to be via a competition between Ras and R-Ras for common downstream effectors or via an inhibition of Ras/Raf-induced MAP kinase activation. Thus, R-Ras and Ras may act in concert to regulate integrin affinity via the activation of distinct downstream effectors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CHO Cells / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinases / genetics
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Cricetinae
  • GTP Phosphohydrolases / genetics
  • GTP Phosphohydrolases / metabolism*
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / metabolism
  • Guanosine Triphosphate / metabolism
  • Integrins / metabolism*
  • Mitogen-Activated Protein Kinase 1
  • Phosphatidylinositol 3-Kinases / metabolism
  • Platelet Glycoprotein GPIIb-IIIa Complex / metabolism
  • Proto-Oncogene Proteins c-raf / genetics
  • Proto-Oncogene Proteins c-raf / metabolism*
  • Suppression, Genetic
  • ral GTP-Binding Proteins
  • ras Proteins / genetics
  • ras Proteins / metabolism*

Substances

  • Integrins
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Guanosine Triphosphate
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-raf
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Mitogen-Activated Protein Kinase 1
  • GTP Phosphohydrolases
  • GTP-Binding Proteins
  • ral GTP-Binding Proteins
  • ras Proteins