DROSOPHILA SIK2 SUBSTRATES

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 胰岛素信号调节高等真核生物的生长和代谢。以前，我们发现胰岛素抑制肝脏激活的盐诱导激酶2（SIK 2），丝氨酸/苏氨酸激酶的应激和能量敏感AMPK家族的成员。 反过来，活化的SIK 2通过CREB辅激活因子TORC的磷酸化和细胞质易位沉默生糖程序。在果蝇中，SIK 2同源物（CG 4290）也在再喂养期间磷酸化TORC; RNAi介导的果蝇神经元中SIK 2的消耗促进饥饿和氧化应激抗性。为了进一步了解SIK 2在禁食代谢中的作用，我们的目标是使用蛋白质组学和遗传学工具来鉴定果蝇中的SIK 2底物。新的SIK 2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，并可能为糖尿病治疗提供新的方法。

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.