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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >MULTIPLE PROTEIN KINASE A-REGULATED EVENTS ARE REQUIRED FOR TRANSCRIPTIONAL INDUCTION BY CAMP
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MULTIPLE PROTEIN KINASE A-REGULATED EVENTS ARE REQUIRED FOR TRANSCRIPTIONAL INDUCTION BY CAMP

机译：通过营地进行转录诱导需要多种蛋白激酶A调节的事件

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摘要

The second messenger cAMP stimulates the expression of numerous genes via the protein kinase A-mediated phosphorylation of the cAMP response element-binding protein (CREB) at Ser-133. Ser-133 phosphorylation, in turn, appears to induce target gene expression by promoting interaction between CREB and CBP, a 265-kDa nuclear phosphoCREB-binding protein. It is unclear, however, whether Ser-133 phosphorylation per se is sufficient for CREB-CBP complex formation and for target gene induction in vivo. Here we examine CREB activity in Jurkat T cells after stimulation of the T-cell receptor (TCR), an event that leads to calcium entry and diacylglycerol production, Triggering of the TCR stimulated Ser-133 phosphorylation of CREB with high stoichiometry, but TCR activation did not promote CREB-CBP complex formation or target gene induction unless suboptimal doses of cAMP agonist were provided as a costimulus. Our results demonstrate that, in addition to mediating Ser-133 phosphorylation of CREB, protein kinase A regulates additional proteins that are required for recruitment of the transcriptional apparatus to cAMP-responsive genes. [References: 17]
机译：第二个信使cAMP通过蛋白激酶A介导的Ser-133处cAMP反应元件结合蛋白（CREB）的磷酸化来刺激众多基因的表达。反过来，Ser-133磷酸化似乎通过促进CREB和CBP（265 kDa核磷酸CREB结合蛋白）之间的相互作用来诱导靶基因表达。然而，尚不清楚Ser-133磷酸化本身是否足以形成CREB-CBP复合物并在体内诱导靶基因。在这里，我们检查了T细胞受体（TCR）刺激后Jurkat T细胞中的CREB活性，该事件导致钙进入和二酰基甘油生成，TCR的触发以高化学计量刺激了CREB的Ser-133磷酸化，但TCR活化除非提供最适剂量的cAMP激动剂，否则不能促进CREB-CBP复合物的形成或靶基因的诱导。我们的研究结果表明，除了介导CREB的Ser-133磷酸化外，蛋白激酶A还调节转录设备募集到cAMP响应基因所需的其他蛋白。 [参考：17]

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