Urban Jörg, Soulard Alexandre, Huber Alexandre, Lippman Soyeon, Mukhopadhyay Debdyuti, Deloche Olivier, Wanke Valeria, Anrather Dorothea, Ammerer Gustav, Riezman Howard, Broach James R, De Virgilio Claudio, Hall Michael N, Loewith Robbie
Department of Molecular Biology, University of Geneva, Geneva, CH-1211, Switzerland.
Mol Cell. 2007 Jun 8;26(5):663-74. doi: 10.1016/j.molcel.2007.04.020.
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 G0 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.
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中发挥作用：TORC1和TORC2。这些保守的复合物响应细胞内和细胞外信号，调节细胞生长的许多不同方面。在此，我们报告AGC激酶Sch9是酵母TORC1的一个底物。Sch9 C末端的六个氨基酸被TORC1直接磷酸化。这些残基的磷酸化在雷帕霉素处理以及碳或氮饥饿时消失，并在施加渗透压、氧化或热应激后短暂降低。Sch9的活性需要TORC1依赖性磷酸化，用天冬氨酸/谷氨酸取代被TORC1磷酸化的残基会使Sch9的活性不依赖于TORC1。TORC1要正确调节核糖体生物发生、翻译起始和进入G0期需要Sch9，但对Gln3依赖性基因的表达则不需要。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。
