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Vol. 10, Issue 6, 1799-1809, June 1999
and§
*Department of Respiratory Medicine, University of Edinburgh
Medical School, Edinburgh EH8 9AG, United Kingdom;
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.
Department of Vascular Biology, The Scripps Research
Institute, La Jolla, California 92037; and Signal
Transduction Laboratory, Imperial Cancer Research Fund, London WC2A
3PX, United Kingdom
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