Recent advances in the regulation of the TOR pathway by insulin and nutrients
Recent advances in the regulation of the TOR pathway by insulin and nutrients
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DOI：
10.1097/00075197-200501000-00010
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发表时间：
2005-01-01
影响因子：
3.1
通讯作者：
Ortiz-Vega, S
中科院分区：
文献类型：
--
作者：
Avruch, J;Lin, YS;Ortiz-Vega, S
综述目的本文的目的是总结对雷帕霉素 (TOR) 靶点调节的最新进展，雷帕霉素是一种蛋白激酶，由胰岛素、氨基酸和能量充足性独立调节，参与控制细胞生长的蛋白质合成成分。最近的发现主要在两个领域发现：果蝇的遗传研究和哺乳动物系统的研究已经确定了结节性硬化症蛋白复合物的成分，该复合物是蛋白质的异二聚体Hamartin 和 Tuberin 作为 TOR 信号传导的抑制剂，作为胰岛素/IGF-1 信号转导途径通过蛋白激酶 PKB 以及细胞能量状态通过 AMP 激活的蛋白激酶调节 TOR 信号传导的主要靶标。反过来，结节性硬化症蛋白复合物的抑制作用已被证明是通过其灭活小型 ras 样 GTP 酶 Rheb 的能力介导的。第二个进展是通过鉴定 TOR 相关蛋白 raptor 来实现的，它是 TOR 复合物不可或缺的底物结合亚基，也是雷帕霉素和氨基酸缺乏对 TOR 信号传导的抑制作用汇聚的位点。总结这些发现使我们更进一步了解营养物和胰岛素如何协调蛋白质合成以调节合成代谢细胞生长。
Purpose of Review The aim of this article is to summarize recent advances in the understanding of the regulation of the target of rapamycin (TOR), a protein kinase that is regulated independently by insulin, amino acids and energy sufficiency and which participates in the control of the component of protein synthesis responsible for cell growth.Recent findings These have been found in two major areas: genetic studies in Drosophila followed by studies in mammalian systems have identified the components of the Tuberous Sclerosis protein complex, a heterodimer of the proteins Hamartin and Tuberin, as inhibitors of TOR signaling, and as the major targets by which the insulin/IGF-1 signal transduction pathway, through the protein kinase PKB, and the energy status of the cell, through the AMP-activated protein kinase, regulate the TOR signaling. In turn, the inhibitory action of the tuberous sclerosis protein complex has been shown to be mediated by its ability to deactivate the small, ras-like GTPase Rheb. A second advance has been achieved by the identification of the TOR-associated protein raptor, as an indispensable substrate binding subunit of the TOR complex, and as the site at which the inhibitory effects on TOR signaling of rapamycin and amino acid deficiency converge.Summary These findings bring us closer to the understanding of how nutrients and insulin coordinate protein synthesis to regulate anabolic cell growth.