Biozentrum, University of Basel, Spitalstrasse 41, 4056 Basel, Switzerland.
Biozentrum, University of Basel, Spitalstrasse 41, 4056 Basel, Switzerland.
Cell. 2022 May 26;185(11):1814-1836. doi: 10.1016/j.cell.2022.04.013. Epub 2022 May 16.
The target of rapamycin (TOR), discovered 30 years ago, is a highly conserved serine/threonine protein kinase that plays a central role in regulating cell growth and metabolism. It is activated by nutrients, growth factors, and cellular energy. TOR forms two structurally and functionally distinct complexes, TORC1 and TORC2. TOR signaling activates cell growth, defined as an increase in biomass, by stimulating anabolic metabolism while inhibiting catabolic processes. With emphasis on mammalian TOR (mTOR), we comprehensively reviewed the literature and identified all reported direct substrates. In the context of recent structural information, we discuss how mTORC1 and mTORC2, despite having a common catalytic subunit, phosphorylate distinct substrates. We conclude that the two complexes recruit different substrates to phosphorylate a common, minimal motif.
雷帕霉素靶蛋白（TOR）于 30 年前被发现，是一种高度保守的丝氨酸/苏氨酸蛋白激酶，在调节细胞生长和代谢方面发挥着核心作用。它受营养物质、生长因子和细胞能量的激活。TOR 形成两种结构和功能上不同的复合物，TORC1 和 TORC2。TOR 信号通过刺激合成代谢同时抑制分解代谢过程来激活细胞生长，即生物量的增加。我们重点介绍了哺乳动物 TOR（mTOR），全面回顾了文献并确定了所有报道的直接底物。根据最近的结构信息，我们讨论了尽管 mTORC1 和 mTORC2 具有共同的催化亚基，但它们如何磷酸化不同的底物。我们的结论是，这两个复合物募集不同的底物来磷酸化一个共同的、最小的基序。
