Vascular Medicine Research Unit, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
BMB Rep. 2011 Aug;44(8):506-11. doi: 10.5483/bmbrep.2011.44.8.506.
Mammalian Target of Rapamycin (mTOR) is a serine/threonine kinase and that forms two multiprotein complexes known as the mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). mTOR regulates cell growth, proliferation and survival. mTORC1 is composed of the mTOR catalytic subunit and three associated proteins: raptor, mLST8/GβL and PRAS40. mTORC2 contains mTOR, rictor, mLST8/GβL, mSin1, and protor. Here, we discuss mTOR as a promising anti-ischemic agent. It is believed that mTORC2 lies down-stream of Akt and acts as a direct activator of Akt. The different functions of mTOR can be explained by the existence of two distinct mTOR complexes containing unique interacting proteins. The loss of TSC2, which is upstream of mTOR, activates S6K1, promotes cell growth and survival, activates mTOR kinase activities, inhibits mTORC1 and mTORC2 via mTOR inhibitors, and suppresses S6K1 and Akt. Although mTOR signaling pathways are often activated in human diseases, such as cancer, mTOR signaling pathways are deactivated in ischemic diseases. From Drosophila to humans, mTOR is necessary for Ser473 phosphorylation of Akt, and the regulation of Akt-mTOR signaling pathways may have a potential role in ischemic disease. This review evaluates the potential functions of mTOR in ischemic diseases. A novel mTOR-interacting protein deregulates over-expression in ischemic disease, representing a new mechanism for controlling mTOR signaling pathways and potential therapeutic strategies for ischemic diseases.
哺乳动物雷帕霉素靶蛋白（mTOR）是一种丝氨酸/苏氨酸激酶，它形成两个多蛋白复合物，称为 mTOR 复合物 1（mTORC1）和 mTOR 复合物 2（mTORC2）。mTOR 调节细胞生长、增殖和存活。mTORC1 由 mTOR 催化亚基和三个相关蛋白组成：raptor、mLST8/GβL 和 PRAS40。mTORC2 包含 mTOR、rictor、mLST8/GβL、mSin1 和 protor。在这里，我们讨论了 mTOR 作为一种有前途的抗缺血药物。据信，mTORC2 位于 Akt 的下游，作为 Akt 的直接激活剂。mTOR 存在两个不同的 mTOR 复合物，包含独特的相互作用蛋白，这可以解释其不同的功能。mTOR 的上游 TSC2 的缺失激活 S6K1，促进细胞生长和存活，激活 mTOR 激酶活性，通过 mTOR 抑制剂抑制 mTORC1 和 mTORC2，并抑制 S6K1 和 Akt。尽管 mTOR 信号通路在人类疾病（如癌症）中经常被激活，但在缺血性疾病中，mTOR 信号通路被失活。从果蝇到人类，mTOR 是 Akt Ser473 磷酸化所必需的，调节 Akt-mTOR 信号通路可能在缺血性疾病中具有潜在作用。本综述评估了 mTOR 在缺血性疾病中的潜在功能。一种新的 mTOR 相互作用蛋白在缺血性疾病中过度表达失调，代表了一种控制 mTOR 信号通路的新机制，并为缺血性疾病提供了潜在的治疗策略。
