INDUCTION OF CREB MEDIATED GENE EXPRESSION BY CAMP

响应于cAMP刺激，CREB通过cAMP依赖性蛋白激酶（PKA）在Ser 133处磷酸化。 磷酸化CREB部分地通过募集信号依赖性共激活因子CP 300刺激靶基因表达。 除cAMP外，许多第二信使途径包括磷酸肌醇途径也可诱导Ser 133磷酸化。 但是，这些途径似乎并不通过CREB刺激靶基因表达，而PKA提供了刺激CREB激活的额外信号（称为第二事件）。 因此，实验建议的目的是确定第二个事件的机制。具体来说，我将测试两种替代模型：阴性信号对应于KID或KIX中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。 CREB参与细胞的生长、分化、长时程记忆和元记忆的形成等多种生物学过程，了解CREB活性的信号转导通路对这些生物学过程具有重要意义。

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.