Fang Y, Vilella-Bach M, Bachmann R, Flanigan A, Chen J
Department of Cell and Structural Biology, University of Illinois at Urbana-Champaign, 601 South Goodwin Avenue, B107, Urbana, IL 61801, USA.
Science. 2001 Nov 30;294(5548):1942-5. doi: 10.1126/science.1066015.
The mammalian target of rapamycin (mTOR) governs cell growth and proliferation by mediating the mitogen- and nutrient-dependent signal transduction that regulates messenger RNA translation. We identified phosphatidic acid (PA) as a critical component of mTOR signaling. In our study, mitogenic stimulation of mammalian cells led to a phospholipase D-dependent accumulation of cellular PA, which was required for activation of mTOR downstream effectors. PA directly interacted with the domain in mTOR that is targeted by rapamycin, and this interaction was positively correlated with mTOR's ability to activate downstream effectors. The involvement of PA in mTOR signaling reveals an important function of this lipid in signal transduction and protein synthesis, as well as a direct link between mTOR and mitogens. Furthermore, these studies suggest a potential mechanism for the in vivo actions of the immunosuppressant rapamycin.
雷帕霉素的哺乳动物靶点（mTOR）通过介导调节信使核糖核酸翻译的有丝分裂原和营养物质依赖性信号转导来控制细胞生长和增殖。我们确定磷脂酸（PA）是mTOR信号传导的关键组成部分。在我们的研究中，对哺乳动物细胞的有丝分裂原刺激导致细胞PA的磷脂酶D依赖性积累，这是激活mTOR下游效应器所必需的。PA直接与mTOR中被雷帕霉素靶向的结构域相互作用，这种相互作用与mTOR激活下游效应器的能力呈正相关。PA参与mTOR信号传导揭示了这种脂质在信号转导和蛋白质合成中的重要功能，以及mTOR与有丝分裂原之间的直接联系。此外，这些研究提示了免疫抑制剂雷帕霉素体内作用的潜在机制。
