Integrin Activation by R-ras

Expression of a constitutively active R-ras converted two cell lines that grow in suspension into highly adherent cells. There was little change in cell surface expression of integrins, but attachment to surfaces coated with the integrin ligands was greatly enhanced. Cells transfected with activated R-ras bound integrin ligands from solution with higher affinities and assembled severalfold more fibronectin matrix than control transfectants. Introduction of a dominant negative R-ras into adherent cells reduced the adhesiveness of the cells, indicating that endogenous R-ras can control the ligand-binding activity of integrins. These results provide a mechanism for the modulation of integrin ligand-binding activity as well as novel function for R-ras.

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