Rac1 调节 mTORC1 和 mTORC2 的活性，并控制细胞大小。
Rac1 regulates the activity of mTORC1 and mTORC2 and controls cellular size.
机构信息
Department of Medicine, Division of Signal Transduction, Harvard Medical School, Beth Israel Deaconess Medical Center, CLS-417, Boston, MA 02115, USA.
出版信息
Mol Cell. 2011 Apr 8;42(1):50-61. doi: 10.1016/j.molcel.2011.03.017.
Mammalian target of rapamycin (mTOR) is a serine/threonine kinase that exists in two separate complexes, mTORC1 and mTORC2, that function to control cell size and growth in response to growth factors, nutrients, and cellular energy levels. Low molecular weight GTP-binding proteins of the Rheb and Rag families are key regulators of the mTORC1 complex, but regulation of mTORC2 is poorly understood. Here, we report that Rac1, a member of the Rho family of GTPases, is a critical regulator of both mTORC1 and mTORC2 in response to growth-factor stimulation. Deletion of Rac1 in primary cells using an inducible-Cre/Lox approach inhibits basal and growth-factor activation of both mTORC1 and mTORC2. Rac1 appears to bind directly to mTOR and to mediate mTORC1 and mTORC2 localization at specific membranes. Binding of Rac1 to mTOR does not depend on the GTP-bound state of Rac1, but on the integrity of its C-terminal domain. This function of Rac1 provides a means to regulate mTORC1 and mTORC2 simultaneously.
哺乳动物雷帕霉素靶蛋白（mTOR）是一种丝氨酸/苏氨酸激酶，存在于两个独立的复合物中，mTORC1 和 mTORC2，它们的功能是响应生长因子、营养物质和细胞能量水平来控制细胞大小和生长。Rheb 和 Rag 家族的低分子量 GTP 结合蛋白是 mTORC1 复合物的关键调节剂，但 mTORC2 的调节机制尚不清楚。在这里，我们报告 Rac1（Rho 家族 GTP 酶的成员之一）是响应生长因子刺激时 mTORC1 和 mTORC2 的关键调节剂。使用诱导型 Cre/Lox 方法在原代细胞中删除 Rac1 可抑制 mTORC1 和 mTORC2 的基础和生长因子激活。Rac1 似乎直接结合 mTOR 并介导 mTORC1 和 mTORC2 在特定膜上的定位。Rac1 与 mTOR 的结合不依赖于 Rac1 的 GTP 结合状态，而是依赖于其 C 末端结构域的完整性。Rac1 的这种功能提供了一种同时调节 mTORC1 和 mTORC2 的方法。
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