The role of mTOR-mediated signals during haemopoiesis and lineage commitment.
The role of mTOR-mediated signals during haemopoiesis and lineage commitment.
复制标题
DOI：
10.1042/bst20180141
复制
发表时间：
2018-10-19
影响因子：
3.9
通讯作者：
Michie AM
中科院分区：
文献类型：
--
作者：
Malik N;Sansom OJ;Michie AM
雷帕霉素的丝氨酸/苏氨酸蛋白激酶机制靶点（mTOR）已经涉及一系列细胞功能的调节，包括蛋白质和脂质合成、增殖、细胞大小和存活。在这里，我们描述了mTOR在造血过程中的作用mTORC 1和mTORC 2的背景下，不同的复合物，它的功能。使用特异性靶向单个mTOR信号传导组分的条件性转基因小鼠模型以及选择性抑制剂，已经产生了大量的研究，强调了mTOR和单个mTOR复合物在造血谱系定型和发育中所起的关键作用。本文综述了mTOR在胚胎发生和造血中的重要作用，强调了mTORC 1在造血细胞发育早期阶段的重要性，通过调节干细胞增强和自我更新，以及红系和B细胞谱系定型。此外，将在T细胞发育和B细胞成熟期间探索mTORC 2在造血中的相对独立的作用。总的来说，这篇综述旨在强调mTOR信号转导的功能多样性，并强调这一途径在造血中的重要性。
The serine/threonine protein kinase mechanistic target of rapamycin (mTOR) has been implicated in the regulation of an array of cellular functions including protein and lipid synthesis, proliferation, cell size and survival. Here, we describe the role of mTOR during haemopoiesis within the context of mTORC1 and mTORC2, the distinct complexes in which it functions. The use of conditional transgenic mouse models specifically targeting individual mTOR signalling components, together with selective inhibitors, have generated a significant body of research emphasising the critical roles played by mTOR, and individual mTOR complexes, in haemopoietic lineage commitment and development. This review will describe the profound role of mTOR in embryogenesis and haemopoiesis, underscoring the importance of mTORC1 at the early stages of haemopoietic cell development, through modulation of stem cell potentiation and self-renewal, and erythroid and B cell lineage commitment. Furthermore, the relatively discrete role of mTORC2 in haemopoiesis will be explored during T cell development and B cell maturation. Collectively, this review aims to highlight the functional diversity of mTOR signalling and underline the importance of this pathway in haemopoiesis.