The focal adhesion protein vinexin alpha regulates the phosphorylation and activity of estrogen receptor alpha.
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 alpha and beta (ERalpha and ERbeta), androgen receptor, and glucocorticoid receptor bind in vitro to vinexin alpha, a multiple SH3 motif-containing protein associated with the cytoskeleton. The SH3 domains are not involved in this interaction. Furthermore, we demonstrate that vinexin alpha 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 alpha and ERalpha results in a loss of ERalpha phosphorylation on serines and the partial redistribution of vinexin alpha into the nucleus, where it colocalizes with ERalpha. 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.
Tujague
Michel
M
Department of Biosciences, Karolinska Institutet, Novum, S-14157 Huddinge, Sweden. michel.tujague@biosci.ki.se
Thomsen
Jane S
JS
Mizuki
Kazuhito
K
Sadek
Christine M
CM
Gustafsson
Jan-Ake
JA
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D047628:Estrogen Receptor alpha; D022001:Focal Adhesions / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D011960:Receptors, Estrogen / Q000378:metabolism*; D016415:Sequence Alignment; D015398:Signal Transduction; D015533:Transcriptional Activation
D048868:Adaptor Proteins, Signal Transducing; D047628:Estrogen Receptor alpha; D009124:Muscle Proteins; D011960:Receptors, Estrogen; C486523:SORBS3 protein, human; C117452:Sorbs3 protein, mouse