Kino Tomoshige, Tiulpakov Anatoly, Ichijo Takamasa, Chheng Ly, Kozasa Tohru, Chrousos George P
Reproductive Biology and Medicine Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
J Cell Biol. 2005 Jun 20;169(6):885-96. doi: 10.1083/jcb.200409150. Epub 2005 Jun 13.
Extracellular stimuli that activate cell surface receptors modulate glucocorticoid actions via as yet unclear mechanisms. Here, we report that the guanine nucleotide-binding protein (G protein)-coupled receptor-activated WD-repeat Gbeta interacts with the glucocorticoid receptor (GR), comigrates with it into the nucleus and suppresses GR-induced transactivation of the glucocorticoid-responsive genes. Association of Ggamma with Gbeta is necessary for this action of Gbeta. Both endogenous and enhanced green fluorescent protein (EGFP)-fused Gbeta2 and Ggamma2 proteins were detected in the nucleus at baseline, whereas a fraction of EGFP-Gbeta2 and DsRed2-GR comigrated to the nucleus or the plasma membrane, depending on the exposure of cells to dexamethasone or somatostatin, respectively. Gbeta2 was associated with GR/glucocorticoid response elements (GREs) in vivo and suppressed activation function-2-directed transcriptional activity of the GR. We conclude that the Gbetagamma complex interacts with the GR and suppresses its transcriptional activity by associating with the transcriptional complex formed on GR-responsive promoters.
激活细胞表面受体的细胞外刺激通过尚不清楚的机制调节糖皮质激素的作用。在此，我们报告鸟嘌呤核苷酸结合蛋白（G蛋白）偶联受体激活的WD重复Gβ与糖皮质激素受体（GR）相互作用，与其一起迁移到细胞核中，并抑制GR诱导的糖皮质激素反应基因的反式激活。Gγ与Gβ的结合对于Gβ的这一作用是必需的。在基线时，在内源性和增强型绿色荧光蛋白（EGFP）融合的Gβ2和Gγ2蛋白均在细胞核中被检测到，而一部分EGFP-Gβ2和DsRed2-GR分别根据细胞是否暴露于地塞米松或生长抑素而迁移到细胞核或质膜。Gβ2在体内与GR/糖皮质激素反应元件（GREs）相关联，并抑制GR的激活功能-2指导的转录活性。我们得出结论，Gβγ复合物与GR相互作用，并通过与在GR反应性启动子上形成的转录复合物结合来抑制其转录活性。
