激酶和蛋白磷酸化作为类固醇激素作用的调节因子。

Nancy L Weigel, Nicole L Moore
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引用次数: 66

摘要

尽管类固醇激素受体激活的主要信号是激素的结合,但越来越多的证据表明,细胞信号通路的活性以及这些转录因子及其共调节因子的磷酸化状态决定了对激素的总体反应。在某些情况下,增强的细胞信号传导足以在缺乏类固醇的介质中引起受体的激活。类固醇受体是多种激酶的靶标。许多磷酸化位点包含Ser/Thr-Pro基序,涉及脯氨酸定向激酶,如细胞周期蛋白依赖性激酶和丝裂原活化激酶(MAPK)在受体磷酸化中的作用。虽然一些位点是组成性磷酸化的,但其他位点是在激素的作用下磷酸化的。还有一些仅在响应特定细胞信号通路时磷酸化。特定位点的磷酸化不仅与整体转录活性有关,还与核定位、蛋白质稳定性和DNA结合有关。关于磷酸化在共调节功能中的作用的研究比较有限,但现在已经确定,其中许多是高度磷酸化的,磷酸化调节其功能。有充分的证据表明,受体和共调节因子中的一些磷酸化位点是多种信号通路的靶点。单个位点既与增强受体活性的功能有关,也与抑制活性的功能有关。因此,类固醇受体磷酸化与共调节因子的表达水平和磷酸化状态的特定组合将决定被调控的基因和生物反应。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Kinases and protein phosphorylation as regulators of steroid hormone action.

Kinases and protein phosphorylation as regulators of steroid hormone action.

Kinases and protein phosphorylation as regulators of steroid hormone action.

Although the primary signal for the activation of steroid hormone receptors is binding of hormone, there is increasing evidence that the activities of cell signaling pathways and the phosphorylation status of these transcription factors and their coregulators determine the overall response to the hormone. In some cases, enhanced cell signaling is sufficient to cause activation of receptors in medium depleted of steroids. Steroid receptors are targets for multiple kinases. Many of the phosphorylation sites contain Ser/Thr-Pro motifs implicating proline-directed kinases such as the cyclin-dependent kinases and the mitogen-activated kinases (MAPK) in receptor phosphorylation. Although some sites are constitutively phosphorylated, others are phosphorylated in response to hormone. Still others are only phosphorylated in response to specific cell signaling pathways. Phosphorylation of specific sites has been implicated not only in overall transcriptional activity, but also in nuclear localization, protein stability, and DNA binding. The studies of the roles of phosphorylation in coregulator function are more limited, but it is now well established that many of them are highly phosphorylated and that phosphorylation regulates their function. There is good evidence that some of the phosphorylation sites in the receptors and coregulators are targets of multiple signaling pathways. Individual sites have been associated both with functions that enhance the activity of the receptor, as well as with functions that inhibit activity. Thus, the specific combinations of phosphorylations of the steroid receptor combined with the expression levels and phosphorylation status of coregulators will determine the genes regulated and the biological response.

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