Phosphatidic acid-mediated mitogenic activation of mTOR signaling
Phosphatidic acid-mediated mitogenic activation of mTOR signaling
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DOI：
10.1126/science.1066015
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发表时间：
2001-11-30
期刊：
影响因子：
56.9
通讯作者：
Chen, J
中科院分区：
文献类型：
--
作者：
Fang, YM;Vilella-Bach, M;Chen, J
哺乳动物雷帕霉素靶蛋白（mTOR）通过介导调节信使RNA翻译的丝裂原和营养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信号传导的关键组分。在我们的研究中，哺乳动物细胞的促有丝分裂刺激导致细胞PA的磷脂酶D依赖性积累，这是激活mTOR下游效应子所必需的。PA直接与雷帕霉素靶向的mTOR结构域相互作用，这种相互作用与mTOR激活下游效应子的能力呈正相关。PA参与mTOR信号转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和有丝分裂原之间的直接联系。此外，这些研究表明免疫抑制剂雷帕霉素的体内作用的潜在机制。
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.