Control of B lymphocyte development and functions by the mTOR signaling pathways.

Control of B lymphocyte development and functions by the mTOR signaling pathways.
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DOI:
10.1016/j.cytogfr.2017.04.005
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发表时间:
2017-06
影响因子:
13
通讯作者:
Iritani BM
Iritani BM
中科院分区:
医学2区
文献类型:
--
作者:
Iwata TN;Ramírez-Komo JA;Park H;Iritani BM

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雷帕霉素的机制靶点(mTOR)是一种丝氨酸/苏氨酸激酶,最初被发现作为免疫抑制剂雷帕霉素的分子靶点。mTOR形成两种组成和功能不同的复合物,mTORC 1和mTORC 2,它们对于协调营养、能量、氧和生长因子的可用性与细胞生长、增殖和存活至关重要。最近的研究已经确定了mTORC 1和mTORC 2在控制B细胞发育、分化和功能中的关键的、非冗余的作用,并且已经强调了滤泡素-Fnip蛋白复合物在调节mTOR和B细胞发育中的新兴作用。在这篇综述中,我们总结了mTOR信号转导的基本机制;描述了mTORC 1,mTORC 2和滤泡蛋白/Fnip 1通路在B细胞发育和功能中的作用;并简要概述了目前针对mTOR的B细胞肿瘤的临床方法。最后,我们强调了几个突出的问题和未来的前景,mTOR在B谱系细胞。
Mechanistic target of rapamycin (mTOR) is a serine/threonine kinase originally discovered as the molecular target of the immunosuppressant rapamycin. mTOR forms two compositionally and functionally distinct complexes, mTORC1 and mTORC2, which are crucial for coordinating nutrient, energy, oxygen, and growth factor availability with cellular growth, proliferation, and survival. Recent studies have identified critical, non-redundant roles for mTORC1 and mTORC2 in controlling B cell development, differentiation, and functions, and have highlighted emerging roles of the Folliculin-Fnip protein complex in regulating mTOR and B cell development. In this review, we summarize the basic mechanisms of mTOR signaling; describe what is known about the roles of mTORC1, mTORC2, and the Folliculin/Fnip1 pathway in B cell development and functions; and briefly outline current clinical approaches for targeting mTOR in B cell neoplasms. We conclude by highlighting a few salient questions and future perspectives regarding mTOR in B lineage cells.
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