INDUCTION OF CREB MEDIATED GENE EXPRESSION BY CAMP

在cAMP刺激下，CREB通过cAMP依赖性蛋白激酶（PKA）在Ser 133位点磷酸化。磷酸化的CREB刺激靶基因表达，部分是通过信号依赖性共激活因子cp300的募集。除cAMP外，包括磷酸-肌醇途径在内的许多第二信使通路均可诱导Ser 133磷酸化。但是，这些途径似乎并没有通过CREB刺激靶基因的表达，这表明PKA提供了一个额外的信号（称为第二事件）来刺激CREB的激活。因此，实验方案旨在确定第二个事件背后的机制。具体来说，我将测试两种替代模型：负信号对应于KID或KIX的磷酸化或去磷酸化事件；2)阴性对应于阻断这两个结构域之间复合物的抑制蛋白。研究表明，CREB涉及不同的生物过程，包括细胞生长、分化、长期记忆和元记忆的形成。了解调节CREB活动的信号转导途径将对这些bi过程具有重要意义。

In response to cAMP stimulation, CREB is phosphorylated at Ser 133 via the cAMP dependent protein kinase (PKA). Phosphorylated CREB stimulates target gene expression, in part, via the recruitment of the signal dependent co-activators C P300. In addition to cAMP, a number of second messenger pathways including the phospho-inositol pathway have been sh induce Ser 133 phosphorylation. But, these pathways do not appear to stimulate target gene expression via CREB, suggesti PKA provides an additional signal (referred as the second event) that stimulates CREB activation. Thus, the experiments proposal are designed to identify the mechanism underlying the second event. Specifically, I will test two alternative models: the negative signal corresponds to a phosphorylation or dephosphorylation event in KID or KIX; 2) that the negative corresponds to an inhibiting protein which blocks complex between these two domains. CREB has been shown to involve different biological processes including cell growth, differentiation, the formation of long-term memory and meta Understand the signal transduction pathways that regulate CREB activities will have important implication for these bi processes.