Lopez G N, Turck C W, Schaufele F, Stallcup M R, Kushner P J
Metabolic Research Unit, Department of Medicine, and Howard Hughes Medical Institute, University of California, San Francisco, California 94143, USA.
J Biol Chem. 2001 Jun 22;276(25):22177-82. doi: 10.1074/jbc.M010718200. Epub 2001 Apr 11.
Promoter-bound steroid receptors activate gene expression by recruiting members of the p160 family of coactivators. Many steroid receptors, most notably the progesterone and estrogen receptors, are regulated both by cognate hormone and independently by growth factors. Here we show that epidermal growth factor regulates the activities of the p160 GRIP1 through the extracellular signal-regulated kinase (ERK) family of mitogen-activated protein kinases. ERKs phosphorylate GRIP1 at a specific site, Ser-736, the integrity of which is required for full growth factor induction of GRIP1 transcriptional activation and coactivator function. We propose that growth factors signal to nuclear receptors in part by targeting the p160 coactivators.
与启动子结合的类固醇受体通过招募p160共激活因子家族成员来激活基因表达。许多类固醇受体，最显著的是孕酮受体和雌激素受体，既受同源激素调节，也受生长因子独立调节。在此我们表明，表皮生长因子通过丝裂原活化蛋白激酶的细胞外信号调节激酶（ERK）家族来调节p160 GRIP1的活性。ERK在一个特定位点Ser-736使GRIP1磷酸化，该位点的完整性对于GRIP1转录激活和共激活因子功能的完全生长因子诱导是必需的。我们提出，生长因子部分通过靶向p160共激活因子向核受体发出信号。
