mTOR 复合物 2 的信号转导和功能。
mTOR complex 2 signaling and functions.
机构信息
Department of Physiology and Biophysics, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ, USA.
出版信息
Cell Cycle. 2011 Jul 15;10(14):2305-16. doi: 10.4161/cc.10.14.16586.
Abstract
The mechanistic target of rapamycin (mTOR) plays a central role in cellular growth and metabolism. mTOR forms two distinct protein complexes, mTORC1 and mTORC2. Much is known about the regulation and functions of mTORC1 due to availability of a natural compound, rapamycin, that inhibits this complex. Studies that define mTORC2 cellular functions and signaling have lagged behind. The development of pharmacological inhibitors that block mTOR kinase activity, and thereby inhibit both mTOR complexes, along with availability of mice with genetic knockouts in mTOR complex components have now provided new insights on mTORC2 function and regulation. Since prolonged effects of rapamycin can also disrupt mTORC2, it is worth re-evaluating the contribution of this less-studied mTOR complex in cancer, metabolic disorders and aging. In this review, we focus on recent developments on mammalian mTORC2 signaling mechanisms and its cellular and tissue-specific functions.
摘要
雷帕霉素靶蛋白（mTOR）在细胞生长和代谢中发挥着核心作用。mTOR 形成两个不同的蛋白质复合物，mTORC1 和 mTORC2。由于天然化合物雷帕霉素的存在，mTORC1 的调控和功能已被广泛研究，雷帕霉素可以抑制该复合物。mTORC2 的细胞功能和信号转导研究则相对滞后。现在，mTOR 激酶活性的药理学抑制剂的开发，以及 mTOR 复合物成分的基因敲除小鼠的出现，为 mTORC2 的功能和调控提供了新的见解。由于雷帕霉素的长期作用也会破坏 mTORC2，因此值得重新评估这个研究较少的 mTOR 复合物在癌症、代谢紊乱和衰老中的作用。在这篇综述中，我们重点介绍了哺乳动物 mTORC2 信号机制及其细胞和组织特异性功能的最新进展。
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