Sarbassov Dos D, Sabatini David M
Department of Biology, Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
J Biol Chem. 2005 Nov 25;280(47):39505-9. doi: 10.1074/jbc.M506096200. Epub 2005 Sep 23.
The raptor-mTOR protein complex is a key component of a nutrient-sensitive signaling pathway that regulates cell size by controlling the accumulation of cellular mass. How nutrients regulate signaling through the raptor-mTOR complex is not well known. Here we show that a redox-sensitive mechanism regulates the phosphorylation of the raptor-mTOR effector S6K1, the interaction between raptor and mTOR, and the kinase activity of the raptor-mTOR complex. In cells treated with the oxidizing agents diamide or phenylarsine oxide, S6K1 phosphorylation increased and became insensitive to nutrient deprivation. Conversely, the reducing reagent BAL (British anti-Lewisite, also known as 2,3-dimercapto-1-propanol) inhibits S6K1 phosphorylation and stabilizes the interaction of mTOR and raptor to mimic the state of the complex under nutrient-deprived conditions. Our findings suggest that a redox-based signaling mechanism may participate in regulating the nutrient-sensitive raptor-mTOR complex and pathway.
猛禽-mTOR蛋白复合物是营养敏感信号通路的关键组成部分，该信号通路通过控制细胞质量的积累来调节细胞大小。营养物质如何通过猛禽-mTOR复合物调节信号传导尚不清楚。在这里，我们表明一种氧化还原敏感机制调节猛禽-mTOR效应器S6K1的磷酸化、猛禽与mTOR之间的相互作用以及猛禽-mTOR复合物的激酶活性。在用氧化剂二酰胺或苯胂氧化物处理的细胞中，S6K1磷酸化增加且对营养剥夺不敏感。相反，还原试剂BAL（英国抗刘易斯毒气剂，也称为2,3-二巯基-1-丙醇）抑制S6K1磷酸化并稳定mTOR与猛禽的相互作用，以模拟营养剥夺条件下复合物的状态。我们的研究结果表明，基于氧化还原的信号传导机制可能参与调节营养敏感的猛禽-mTOR复合物和信号通路。
