DROSOPHILA TORC ASSOCIATED PROTEINS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 细胞内的第二信使cAMP起饥饿状态信号的作用，它介导了对激素刺激的分解代谢程序的诱导。例如，在禁食的哺乳动物中，葡萄糖平衡是通过cAMP反应的CREB共激活因子TORC2诱导糖异生基因来响应循环中胰腺高血糖素的反应来维持的。在摄食条件下，TORC2被隔离在细胞质中，在cAMP信号的响应下，TORC2被去磷酸化并移位到细胞核，然后它通过与CREB结合在相关启动子上刺激基因表达。为了进一步剖析TORC家族在能量平衡中的作用，我们将使用蛋白质组学和遗传学工具来操纵果蝇的TORC活性。对果蝇TORC相关蛋白的鉴定将为这种共激活因子对环境提示做出反应的机制提供新的见解。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The intracellular second messenger cAMP functions as a starvation state signal, which mediates induction of catabolic programs in response to hormonal stimulation. Glucose balance in fasted mammals is maintained, for example, by induction of gluconeogenic genes by the cAMP responsive CREB coactivator TORC2 in response to elevations in circulating pancreatic glucagon. Sequestered in the cytoplasm under feeding conditions, TORC2 is dephosphorylated and translocated to the nucleus in response to cAMP signaling, whereupon it stimulates gene expression by associating with CREB over relevant promoters. To further dissect the role of the TORC family in energy balance, we will use proteomic and genetic tools to manipulate TORC activity in Drosophila. The identification of Drosophila TORC-associated proteins will provide new insights into the mechanisms by which this coactivator responds to environmental cues.