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mTOR 介导的信号在造血和谱系分化中的作用。

The role of mTOR-mediated signals during haemopoiesis and lineage commitment.

机构信息

Institute of Cancer Sciences, College of Medicine, Veterinary and Life Sciences, University of Glasgow, Glasgow, U.K.

Cancer Research UK Beatson Institute, Garscube Estate, Glasgow, U.K.

出版信息

Biochem Soc Trans. 2018 Oct 19;46(5):1313-1324. doi: 10.1042/BST20180141. Epub 2018 Aug 28.

Abstract

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.

摘要

丝氨酸/苏氨酸蛋白激酶雷帕霉素靶蛋白(mTOR)已被牵涉到调节一系列细胞功能,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 mTORC1 和 mTORC2 这两个不同的复合物中的作用,即在造血过程中的作用。使用特异性靶向单个 mTOR 信号转导成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 复合物在造血谱系的承诺和发展中所起的关键作用。这篇综述将描述 mTOR 在胚胎发生和造血中的深刻作用,强调 mTORC1 在造血细胞发育的早期阶段通过调节干细胞潜能和自我更新以及红系和 B 细胞谱系的承诺的重要性。此外,mTORC2 在 T 细胞发育和 B 细胞成熟过程中的相对离散作用将被探索。总的来说,这篇综述旨在强调 mTOR 信号的功能多样性,并强调该途径在造血中的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7647/6195642/dd38b9587f58/BST-46-1313-g0001.jpg

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