This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor 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.
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