作者
Biao Wang, Jason Goode, Jennifer Best, Jodi Meltzer, Pablo E Schilman, Jian Chen, Dan Garza, John B Thomas, Marc Montminy
发表日期
2008/5/7
期刊
Cell metabolism
卷号
7
期号
5
页码范围
434-444
出版商
Elsevier
简介
In fasted mammals, glucose homeostasis is maintained through induction of the cAMP response element-binding protein (CREB) coactivator transducer of regulated CREB activity 2 (TORC2), which stimulates the gluconeogenic program in concert with the forkhead factor FOXO1. Here we show that starvation also triggers TORC activation in Drosophila, where it maintains energy balance through induction of CREB target genes in the brain. TORC mutant flies have reduced glycogen and lipid stores and are sensitive to starvation and oxidative stress. Neuronal TORC expression rescued stress sensitivity as well as CREB target gene expression in TORC mutants. During refeeding, increases in insulin signaling inhibited TORC activity through the salt-inducible kinase 2 (SIK2)-mediated phosphorylation and subsequent degradation of TORC. Depletion of neuronal SIK2 increased TORC activity and enhanced stress …
引用总数
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