Growing knowledge of the mTOR signaling network.
Growing knowledge of the mTOR signaling network.
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DOI：
10.1016/j.semcdb.2014.09.011
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发表时间：
2014-12
影响因子：
7.3
通讯作者：
Fingar, Diane C.
中科院分区：
文献类型：
--
作者：
Huang, Kezhen;Fingar, Diane C.
激酶mTOR（雷帕霉素的机制靶点）整合了不同的环境信号，并将这些信号转化为适当的细胞反应。mTOR形成至少两种功能不同的信号传导复合物mTOR复合物1（mTORC 1）和mTOR复合物2（mTORC 2）的催化核心。mTORC 1促进合成代谢细胞代谢，以响应生长因子、营养素和能量，并作为细胞生长的主控制器发挥作用。虽然对mTORC 2的了解比mTORC 1少得多，但mTORC 2响应生长因子并控制细胞代谢、细胞存活和肌动蛋白细胞骨架的组织。mTOR在与肿瘤发生、代谢、免疫功能和衰老相关的细胞过程中起关键作用。因此，异常的mTOR信号传导导致无数的疾病状态，医生使用mTORC 1抑制剂（雷帕霉素和类似物）治疗几种病理状况。mTOR抑制的临床效用强调了mTOR在生物体生理学中的重要作用。在这里，我们回顾了我们不断增长的知识，细胞mTOR调节不同的上游信号（如生长因子;氨基酸;能源）和mTORC 1如何整合这些信号，以影响适当的下游信号，更强调mTORC 1 mTORC 2。我们强调mTORC 1和相关因子的动态亚细胞定位是控制mTORC 1活性和功能的重要机制。我们将广泛涵盖mTORC 1控制的主要细胞功能。虽然在过去的十年中，关于mTOR在复杂细胞信号网络中的调节和功能已经取得了重大进展，但仍有许多重要的发现有待发现。
The kinase mTOR (mechanistic target of rapamycin) integrates diverse environmental signals and translates these cues into appropriate cellular responses. mTOR forms the catalytic core of at least two functionally distinct signaling complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). mTORC1 promotes anabolic cellular metabolism in response to growth factors, nutrients, and energy and functions as a master controller of cell growth. While significantly less well understood than mTORC1, mTORC2 responds to growth factors and controls cell metabolism, cell survival, and the organization of the actin cytoskeleton. mTOR plays critical roles in cellular processes related to tumorigenesis, metabolism, immune function, and aging. Consequently, aberrant mTOR signaling contributes to myriad disease states, and physicians employ mTORC1 inhibitors (rapamycin and analogs) for several pathological conditions. The clinical utility of mTOR inhibition underscores the important role of mTOR in organismal physiology. Here we review our growing knowledge of cellular mTOR regulation by diverse upstream signals (e.g. growth factors; amino acids; energy) and how mTORC1 integrates these signals to effect appropriate downstream signaling, with a greater emphasis on mTORC1 over mTORC2. We highlight dynamic subcellular localization of mTORC1 and associated factors as an important mechanism for control of mTORC1 activity and function. We will cover major cellular functions controlled by mTORC1 broadly. While significant advances have been made in the last decade regarding the regulation and function of mTOR within complex cell signaling networks, many important findings remain to be discovered.
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影响因子：
64.5
作者：
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通讯作者：
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作者：
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DOI：
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发表时间：
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