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Vinculin is an actin-binding protein present at cell-matrix and cell-cell adhesions, which plays a critical role in bearing force experienced by cells and dissipating it onto the cytoskeleton. Recently, we identified a key tyrosine residue, Y822, whose phosphorylation plays a critical role in force transmission at cell-cell adhesions. The role of Y822 in human cancer remains unknown, even though Y822 is mutated to Y822C in uterine cancers. Here, we investigated the effect of this amino acid substitution and that of a phosphodeficient Y822F vinculin in cancer cells. We observed that the presence of the Y822C mutation led to cells that proliferate and migrate more rapidly and contained smaller focal adhesions when compared to cells with wild-type vinculin. In contrast, the presence of the Y822F mutation led to highly spread cells with larger focal adhesions and increased contractility. Furthermore, we provide evidence that Y822C vinculin forms a disulfide bond with paxillin, accounting for some of the elevated phosphorylated paxillin recruitment. Taken together, these data suggest that vinculin Y822 modulates the recruitment of ligands. [ABSTRACT FROM AUTHOR]

The tyrosine kinase c-Abl, activated by growth factors and Src family kinases, has a role in the cellular response to platelet-derived growth factor (PDGF). A membrane pool of c-Abl has been activated by PDGF and another growth factor, epidermal growth factor, EGF, in fibroblasts. Data show c-Abl to be a downstream target of activated receptor tyrosine kinases, to have a role in cytoskeletal reorganization after PDGF stimulation.

The ability of cells to tightly adhere to one another and to the extracellular matrix is fundamentally important in numerous biological processes, including embryogenesis, wound healing and maintenance of tissue integrity. Vinculin, a protein localized at the cytoplasmic face of call-matrix and cell-cell adhesions, is required for strong cell adhesion. Two new crystal structures reveal that vinculin exhibits a high degree of structural plasticity upon ligand binding that might promote rapid changes in cell adhesion.