The Focal Adhesion Protein Vinexin α Regulates the Phosphorylation and Activity of Estrogen Receptor α

Steroid receptors are transcription factors that regulate hormone-responsive genes and whose activity is controlled by their interaction with numerous other proteins. Observations reported here reveal that estrogen receptors α and β (ERα and ERβ), androgen receptor, and glucocorticoid receptor bind in vitro to vinexin α, a multiple SH3 motif-containing protein associated with the cytoskeleton. The SH3 domains are not involved in this interaction. Furthermore, we demonstrate that vinexin α stimulates the ligand-induced transactivation function of these receptors, although it is devoid of intrinsic transcriptional activity when tethered to DNA. In addition, the ectopic coexpression of vinexin α and ERα results in a loss of ERα phosphorylation on serines and the partial redistribution of vinexin α into the nucleus, where it colocalizes with ERα. These results establish a new model of transcriptional regulation where components of the cell-cell and cell-substrate adhesion complexes can regulate the phosphorylation and activity of steroid receptors.