DROSOPHILA SIK2 SUBSTRATES

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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.