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亮氨酸在氨基酸对mTOR的调节中的作用:结构活性研究的启示

Role of leucine in the regulation of mTOR by amino acids: revelations from structure-activity studies.

作者信息

Lynch C J

机构信息

Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA.

出版信息

J Nutr. 2001 Mar;131(3):861S-865S. doi: 10.1093/jn/131.3.861S.

DOI:10.1093/jn/131.3.861S
PMID:11238775
Abstract

In this study an overview is presented of the mTOR signaling pathway and its regulation by amino acids, particularly L-leucine. Our laboratory is studying amino acid regulation of mTOR in adipocytes. Potential roles for mTOR in adipocytes that were previously posited include hypertrophic growth, leptin secretion, protein synthesis and adipose tissue morphogenesis. A current area of interest in the field is how amino acids regulate mTOR and which amino acids are regulatory. Revelations concerning mechanism and recognition are emerging from different laboratories that examined the structural requirements for stimulation and inhibition of the mTOR signaling pathway by leucine and amino acid analogs. In adipocytes and some other cell types, leucine appears to be the main regulatory amino acid. However, this is not uniformly the case. In those cells where mTOR is regulated by several amino acids, there is evidence that the mechanism of mTOR activation may be different from cells where mainly leucine is regulatory. Furthermore, in tissues where leucine regulates mTOR, the possible existence of different tissue-specific leucine recognition sites may be indicated.

摘要

在本研究中,我们概述了mTOR信号通路及其受氨基酸(特别是L-亮氨酸)调控的情况。我们实验室正在研究脂肪细胞中氨基酸对mTOR的调控作用。先前推测mTOR在脂肪细胞中的潜在作用包括肥大生长、瘦素分泌、蛋白质合成以及脂肪组织形态发生。该领域当前感兴趣的一个方面是氨基酸如何调控mTOR以及哪些氨基酸具有调控作用。不同实验室对亮氨酸和氨基酸类似物刺激和抑制mTOR信号通路的结构要求进行了研究,有关机制和识别的新发现不断涌现。在脂肪细胞和其他一些细胞类型中,亮氨酸似乎是主要的调控氨基酸。然而,情况并非一概如此。在那些mTOR受多种氨基酸调控的细胞中,有证据表明mTOR激活机制可能与主要由亮氨酸调控的细胞不同。此外,在亮氨酸调控mTOR的组织中,可能存在不同的组织特异性亮氨酸识别位点。

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