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

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-l suppress integ rin activation. In this study we explored the relationship between Pas and the closely related small GTP-binding protein R-Ras in modulating the integ rin affinity state. We found that R-Ras does not seem to be a direct activa tor of integrins in Chinese hamster ovary cells. However, we observed that GTP-bound R-Ras strongly antagonizes the Ras/Raf-initiated integrin suppres sion 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 down stream effecters or via an inhibition of Ras/Raf-induced MAP kinase activat ion. Thus, R-Ras and Ras may act in concert to regulate integrin affinity v ia the activation of distinct downstream effecters.