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
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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CHO Cells / metabolism
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Calcium-Calmodulin-Dependent Protein Kinases / genetics
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism
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Cricetinae
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GTP Phosphohydrolases / genetics
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GTP Phosphohydrolases / metabolism*
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GTP-Binding Proteins / genetics
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GTP-Binding Proteins / metabolism
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Guanosine Triphosphate / metabolism
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Integrins / metabolism*
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Mitogen-Activated Protein Kinase 1
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Phosphatidylinositol 3-Kinases / metabolism
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Platelet Glycoprotein GPIIb-IIIa Complex / metabolism
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Proto-Oncogene Proteins c-raf / genetics
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Proto-Oncogene Proteins c-raf / metabolism*
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Suppression, Genetic
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ral GTP-Binding Proteins
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ras Proteins / genetics
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ras Proteins / metabolism*
Substances
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Integrins
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Platelet Glycoprotein GPIIb-IIIa Complex
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Guanosine Triphosphate
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Phosphatidylinositol 3-Kinases
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Proto-Oncogene Proteins c-raf
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Calcium-Calmodulin-Dependent Protein Kinases
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Mitogen-Activated Protein Kinase 1
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GTP Phosphohydrolases
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GTP-Binding Proteins
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ral GTP-Binding Proteins
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ras Proteins