Rapid recruitment of p120RasGAP and its associated protein, p190RhoGAP, to the cytoskeleton during integrin mediated cell-substrate interaction.

The interaction of cells with their substrate triggers cascades of signal transduction that result in profound changes in cell morphology. The nature of these signals and how they are integrated to orchestrate changes in cell shape are beginning to be elucidated. In particular, adhesive interactions between cells and their substrate, mediated by cell-surface integrins and extracellular matrix (ECM) proteins, appear to result in massive rearrangement of the cell cytoskeleton via the small G-protein, Rho. Here we show that in mouse fibroblasts, the interaction between cells and their substrate results in the rapid recruitment to the cytoskeleton of RasGAP (p120RasGAP), its associated protein of 190 kilodaltons, the GTPase activating protein for RhoA (p190RhoGAP) and the focal adhesion kinase (p125FAK). Similar results were obtained when cells were plated on ECM proteins, such as fibronectin, suggesting that the phenomenon is integrin mediated. These studies suggest that in fibroblasts, cell-substrate interaction triggered by integrin engagement result in the recruitment to the cytoskeleton of signaling molecules such as p120RasGAP, p190RhoGAP and p125FAK and may be involved in the formation of membrane cytoskeleton-associated signaling complexes that are important in cytoarchitectural reorganization.