Division of Signal Transduction, Beth Israel Deaconess Medical Center, Systems Biology Department, Harvard Medical School, Boston, Massachusetts 02115, USA.
Nat Cell Biol. 2013 Jun;15(6):555-64. doi: 10.1038/ncb2763.
Flux through metabolic pathways is inherently sensitive to the levels of specific substrates and products, but cellular metabolism is also managed by integrated control mechanisms that sense the nutrient and energy status of a cell or organism. The mechanistic target of rapamycin complex 1 (mTORC1), a protein kinase complex ubiquitous to eukaryotic cells, has emerged as a critical signalling node that links nutrient sensing to the coordinated regulation of cellular metabolism. Here, we discuss the role of mTORC1 as a conduit between cellular growth conditions and the anabolic processes that promote cell growth. The emerging network of signalling pathways through which mTORC1 integrates systemic signals (secreted growth factors) with local signals (cellular nutrients - amino acids, glucose and oxygen - and energy, ATP) is detailed. Our expanding understanding of the regulatory network upstream of mTORC1 provides molecular insights into the integrated sensing mechanisms by which diverse cellular signals converge to control cell physiology.
代谢途径中的通量本质上对特定底物和产物的水平敏感,但细胞代谢也受到整合控制机制的管理,这些机制可以感知细胞或生物体的营养和能量状态。雷帕霉素靶蛋白复合物 1(mTORC1)是一种普遍存在于真核细胞中的蛋白激酶复合物,已成为一个关键的信号节点,将营养感应与促进细胞生长的细胞代谢的协调调节联系起来。在这里,我们讨论了 mTORC1 作为细胞生长条件与促进细胞生长的合成代谢过程之间的传导途径的作用。详细描述了 mTORC1 整合系统信号(分泌生长因子)与局部信号(细胞营养物质 - 氨基酸、葡萄糖和氧气 - 和能量,ATP)的信号通路网络。我们对 mTORC1 上游调控网络的不断扩展的理解,为多种细胞信号如何汇聚以控制细胞生理学的综合感应机制提供了分子见解。