Vlahakis Ariadne, Powers Ted
a Department of Molecular and Cellular Biology; College of Biological Sciences ; University of California, Davis ; Davis , CA USA.
Autophagy. 2014;10(11):2085-6. doi: 10.4161/auto.36262.
The conserved target of rapamycin (TOR) kinase is a central regulator of cell growth in response to nutrient availability. TOR forms 2 structurally and functionally distinct complexes, TORC1 and TORC2, and negatively regulates autophagy via TORC1. Here we demonstrate TOR also operates independently through the TORC2 signaling pathway to promote autophagy upon amino acid limitation. Under these conditions, TORC2, through its downstream target kinase Ypk1, inhibits the Ca(2+)- and Cmd1/calmodulin-dependent phosphatase, calcineurin, to enable the activation of the amino acid-sensing EIF2S1/eIF2α kinase, Gcn2, and promote autophagy. Thus TORC2 signaling regulates autophagy in a pathway distinct from TORC1 to provide a tunable response to the cellular metabolic state.
保守的雷帕霉素靶蛋白(TOR)激酶是细胞生长响应营养可利用性的核心调节因子。TOR形成两种结构和功能不同的复合物,即TORC1和TORC2,并通过TORC1负向调节自噬。在此,我们证明TOR也通过TORC2信号通路独立发挥作用,在氨基酸限制时促进自噬。在这些条件下,TORC2通过其下游靶激酶Ypk1抑制Ca²⁺和Cmd1/钙调蛋白依赖性磷酸酶钙调神经磷酸酶,从而激活氨基酸感应EIF2S1/eIF2α激酶Gcn2并促进自噬。因此,TORC2信号通路通过一条不同于TORC1的途径调节自噬,以对细胞代谢状态提供可调节的反应。