Wang Yuxiang, Feng Hui, Bi Cheng, Zhu Liyin, Pollard Jeffrey W, Chen Bo
School of Life Science and National Key Laboratory of Genetic Engineering, Fudan University, Shanghai 200433, PR China.
FEBS Lett. 2007 Jun 26;581(16):3069-75. doi: 10.1016/j.febslet.2007.05.072. Epub 2007 Jun 4.
We report that glycogen synthase kinase (GSK)-3beta is phosphorylated at ser9 and inactivated in uterine epithelial cells from E(2)-treated cyclin D1 null mutant mice. Simultaneous administration of P(4) together with E(2) blocked this effect. Pharmacological inhibition of GSK-3beta activity in mice treated with P(4)E(2) reversed the nuclear exclusion of cyclin D2 in the uterine epithelial cells and this caused phosphorylation of Rb protein and progression of cells towards S-phase. Our results indicate that GSK-3beta is a major target of E(2) and P(4) in regulation of cyclin D2 localization in the mouse uterine epithelium.
我们报告，糖原合酶激酶（GSK）-3β在丝氨酸9位点被磷酸化并失活，这发生在经雌激素（E₂）处理的细胞周期蛋白D1基因敲除突变小鼠的子宫上皮细胞中。同时给予孕激素（P₄）和E₂可阻断这一效应。在用P₄和E₂处理的小鼠中，对GSK-3β活性进行药理学抑制可逆转子宫上皮细胞中细胞周期蛋白D2的核排除，这导致视网膜母细胞瘤（Rb）蛋白磷酸化，并使细胞进入S期。我们的结果表明，在调控小鼠子宫上皮细胞中细胞周期蛋白D2的定位方面，GSK-3β是E₂和P₄的主要作用靶点。
