MULTIPLE PROTEIN-KINASE A-REGULATED EVENTS ARE REQUIRED FOR TRANSCRIPTIONAL INDUCTION BY CAMP
MULTIPLE PROTEIN-KINASE A-REGULATED EVENTS ARE REQUIRED FOR TRANSCRIPTIONAL INDUCTION BY CAMP
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DOI：
10.1073/pnas.92.23.10521
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发表时间：
1995-11-07
影响因子：
11.1
通讯作者：
MONTMINY, M
中科院分区：
文献类型：
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作者：
BRINDLE, P;NAKAJIMA, T;MONTMINY, M
第二信使训练营通过Ser-133处的蛋白激酶A介导元素结合蛋白（CREB）的蛋白激酶A介导的磷酸化刺激了许多基因的表达。 Ser-133磷酸化反过来似乎通过促进CREB和CBP之间的相互作用诱导靶基因表达，CREB和CBP是一种265 kDA核磷酸结合蛋白。然而，尚不清楚Ser-133磷酸化本身是否足以足以用于CREB-CBP复合物的形成和体内靶基因诱导。在这里，我们在刺激T细胞受体（TCR）后检查Jurkat T细胞中的CREB活性，该事件导致钙进入和二酰基甘油产生，触发TCR刺激的Ser-133 CREB的CREB具有高stoichiementry，但是TCR激活了TCR激活的CREB。除非提供次优剂量的营地激动剂作为一种costimulus。我们的结果表明，除了介导CREB的Ser-133磷酸化外，蛋白激酶A还调节了募集转录设备所需的其他蛋白质，这些蛋白质是为cAMP响应基因募集的。
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.