从酵母到人类的TOR信号网络。

The TOR signalling network from yeast to man.

作者信息

De Virgilio Claudio, Loewith Robbie

机构信息

Department of Microbiology and Molecular Medicine, University of Geneva, 1211 Geneva 4, Switzerland.

出版信息

Int J Biochem Cell Biol. 2006;38(9):1476-81. doi: 10.1016/j.biocel.2006.02.013. Epub 2006 Mar 9.

DOI:10.1016/j.biocel.2006.02.013

PMID:16647875

Abstract

The target of rapamycin, TOR, is an essential ser/thr protein kinase that functions in two distinct multiprotein complexes, TOR complex 1 and 2. The structure and functions of these complexes have been conserved from yeast to man. TOR complex 1 is inhibited by rapamycin and is thought to couple growth cues to cellular metabolism; TOR complex 2 is not inhibited by rapamycin and appears to regulate spatial aspects of growth such as cell polarity. Work done in a variety of model systems, continues to contribute to our current understanding of this TOR signalling network. Recent studies in flies and mammalian tissue culture cells have elucidated many signalling components upstream of TOR complex 1. These studies also suggest that aberrant mammalian TOR complex 1 signalling contributes to a number of pathologies ranging from metabolic diseases to hyperproliferative disorders and cancers. Consequently the efficacies of rapamycin and related compounds in treating such diseases are being evaluated in clinical trials.

摘要

雷帕霉素靶蛋白（TOR）是一种重要的丝氨酸/苏氨酸蛋白激酶，它在两种不同的多蛋白复合物——TOR复合物1和TOR复合物2中发挥作用。这些复合物的结构和功能从酵母到人类都保守存在。TOR复合物1受雷帕霉素抑制，被认为将生长信号与细胞代谢联系起来；TOR复合物2不受雷帕霉素抑制，似乎调节生长的空间方面，如细胞极性。在各种模型系统中开展的工作，持续为我们当前对这个TOR信号网络的理解做出贡献。最近在果蝇和哺乳动物组织培养细胞中的研究阐明了TOR复合物1上游的许多信号成分。这些研究还表明，异常的哺乳动物TOR复合物1信号传导导致了从代谢疾病到过度增殖性疾病和癌症等多种病理状况。因此，雷帕霉素及相关化合物在治疗此类疾病方面的疗效正在临床试验中进行评估。