Iwata Terri N, Ramírez-Komo Julita A, Park Heon, Iritani Brian M
The Department of Comparative Medicine, University of Washington, Seattle, WA 98195, USA.
The Department of Comparative Medicine, University of Washington, Seattle, WA 98195, USA.
Cytokine Growth Factor Rev. 2017 Jun;35:47-62. doi: 10.1016/j.cytogfr.2017.04.005. Epub 2017 May 22.
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.
雷帕霉素作用机制靶点(mTOR)是一种丝氨酸/苏氨酸激酶,最初作为免疫抑制剂雷帕霉素的分子靶点被发现。mTOR形成两种在组成和功能上截然不同的复合物,即mTORC1和mTORC2,它们对于协调营养物质、能量、氧气和生长因子的可利用性与细胞生长、增殖及存活至关重要。最近的研究已经确定mTORC1和mTORC2在控制B细胞发育、分化和功能方面具有关键的、非冗余的作用,并突出了卵泡抑素 - Fnip蛋白复合物在调节mTOR和B细胞发育中的新作用。在本综述中,我们总结了mTOR信号传导的基本机制;描述了关于mTORC1、mTORC2以及卵泡抑素/Fnip1途径在B细胞发育和功能中的作用的已知信息;并简要概述了目前在B细胞肿瘤中靶向mTOR的临床方法。我们通过强调关于B系细胞中mTOR的一些突出问题和未来展望来结束本文。