DROSOPHILA SIK2 SUBSTRATES

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。 胰岛素信号调节高等真核生物的生长和代谢。先前，我们发现胰岛素抑制肝脏中盐诱导蛋白2(SIK2)的糖异生，SIK2是应激和能量敏感型AMPK家族丝氨酸/苏氨酸蛋白激酶家族的成员。反过来，激活的SIK2通过CREB辅活化子TORC的磷酸化和细胞质易位来沉默糖生成程序。在果蝇中，SIK2同源基因(CG4290)在再摄食过程中也使TORC磷酸化；RNAi介导的SIK2在果蝇神经元中的缺失促进了饥饿和抗氧化应激的抵抗。为了进一步了解SIK2在禁食代谢中的作用，我们的目标是利用蛋白质组学和遗传学工具在果蝇中鉴定SIK2底物。新的SIK2底物的表征将进一步确定胰岛素信号转导的基本调控机制，并可能为糖尿病的治疗提供新的途径。

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. Insulin signaling regulates growth and metabolism in higher eukaryotes. Previously, we found that insulin inhibits gluconeogenesis in liver activation of Salt Inducible Kinase 2 (SIK2), a member of the stress and energy-sensing AMPK family of Ser/Thr kinases. In turn, activated SIK2 silences the glucogeogenic program through phosphorylation and cytoplasmic translocation of the CREB coactivator TORC. In Drosophila, the SIK2 homolog (CG4290) also phosphorylates TORC during refeeding; RNAi mediated depletion of SIK2 in fly neurons promotes starvation and oxidative stress resistance. To further understand the roles of SIK2 in fasting metabolism, we aim to identify SIK2 substrates in Drosophila using proteomic and genetic tools. The characterization of novel SIK2 substrates will further define the basic regulatory mechanisms of insulin signaling, and may provide new approaches in diabetes treatment.