title: The small GTP-binding protein R-Ras can influence integrin activation by antagonizing a Ras/Raf-initiated integrin suppression pathway.
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.
authors.affiliation: Department of Respiratory Medicine, University of Edinburgh Medical School, Edinburgh EH8 9AG, United Kingdom.
authors.forename: T
authors.initials: T
authors.lastname: Sethi
authors.forename: M H
authors.initials: MH
authors.lastname: Ginsberg
authors.forename: J
authors.initials: J
authors.lastname: Downward
authors.forename: P E
authors.initials: PE
authors.lastname: Hughes
mesh_terms: D000818:Animals; D016466:CHO Cells / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism; D006224:Cricetinae; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D016023:Integrins / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics / Q000378:metabolism*; D013489:Suppression, Genetic; D020725:ral GTP-Binding Proteins; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D016023:Integrins; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D006160:Guanosine Triphosphate; D019869:Phosphatidylinositol 3-Kinases; D019908:Proto-Oncogene Proteins c-raf; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D020725:ral GTP-Binding Proteins; D018631:ras Proteins