Vinculin Y822 is an important determinant of ligand binding.
Journal of cell science(2023)
Abstract
Vinculin is an actin binding protein present at cell-matrix and cell-cell adhesions and 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. Here, we investigated the effect of this amino acid substitution and a phosphodeficient Y822F vinculin in cancer cells. We observed that substitution of Y822C produced cells that proliferate and migrate more rapidly and contained smaller focal adhesions when compared to wildtype vinculin cells. In contrast, substitution of Y822F produced 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.
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Key words
vinculin y822,ligand,important determinant
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