Sch9 is a major target of TORC1 in Saccharomyces cerevisiae
Sch9 is a major target of TORC1 in Saccharomyces cerevisiae
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DOI：
10.1016/j.molcel.2007.04.020
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发表时间：
2007-06-08
期刊：
影响因子：
16
通讯作者：
Loewith, Robbie
中科院分区：
文献类型：
--
作者：
Urban, Jorg;Soulard, Alexandre;Loewith, Robbie
雷帕霉素靶蛋白（TOR）是一种丝氨酸/苏氨酸激酶，在两种不同的多蛋白复合物TORC1和TORC2中发挥作用。这些保守的复合物根据细胞内和细胞外的信号来调控细胞生长的许多不同方面。在此我们报道AGC激酶Sch9是酵母TORC1的一个底物。Sch9的C末端的6个氨基酸被TORC1直接磷酸化。在雷帕霉素处理以及碳源或氮源饥饿时，这些残基的磷酸化消失，并且在施加渗透压、氧化或热应激后会短暂降低。TORC1依赖的磷酸化是Sch9活性所必需的，并且用天冬氨酸/谷氨酸替换被TORC1磷酸化的残基会使Sch9活性不依赖于TORC1。Sch9是TORC1正确调控核糖体生物发生、翻译起始以及进入G₀期所必需的，但不是Gln3依赖基因表达所必需的。我们的结果表明，Sch9的功能类似于哺乳动物TORC1底物S6K1，而不是mTORC2底物PKB/Akt。
The Target of Rapamycin (TOR) protein is a Ser/ Thr kinase that functions in two distinct multiprotein complexes: TORC1 and TORC2. These conserved complexes regulate many different aspects of cell growth in response to intracellular and extracellular cues. Here we report that the AGC kinase Sch9 is a substrate of yeast TORC1. Six amino acids in the C terminus of Sch9 are directly phosphorylated by TORC1. Phosphorylation of these residues is lost upon rapamycin treatment as well as carbon or nitrogen starvation and transiently reduced following application of osmotic, oxidative, or thermal stress. TORC1-dependent phosphorylation is required for Sch9 activity, and replacement of residues phosphorylated by TORC1 with Asp/Glu renders Sch9 activity TORC1 independent. Sch9 is required for TORC1 to properly regulate ribosome biogenesis, translation initiation, and entry into G(0) phase, but not expression of Gln3-dependent genes. Our results suggest that Sch9 functions analogously to the mammalian TORC1 substrate S6K1 rather than the mTORC2 substrate PKB/Akt.