遗传 ›› 2017, Vol. 39 ›› Issue (7): 642-649.doi: 10.16288/j.yczz.17-066

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MST1/2调控先天免疫的功能和机制

周欣(),李伟芸,王红艳()   

  1. 中国科学院上海生命科学研究院生物化学与细胞生物学研究所,中国科学院系统生物学重点实验室,上海 200031
  • 收稿日期:2017-02-28 修回日期:2017-03-22 出版日期:2017-07-20 发布日期:2017-06-28
  • 作者简介:周欣,博士研究生,研究方向：巨噬细胞极性调控。E-mail: zhouxin2013@sibcb.ac.cn|王红艳,博士,研究员,博士生导师,研究方向：免疫细胞和炎症相关疾病的新机制。E-mail: hongyanwang@sibcb.ac.cn
  • 基金资助:
    国家自然科学基金项目(81571617, 31300723, 81671572, 31422018);中科院分子细胞卓越中心成员先导B项目(XDB19000000);科技部重大科学研究项目(2016YFD0500207, 2016YFC0902200)

The roles and mechanisms of MST1/2 in the innate immune response

Xin Zhou(),Weiyun Li,Hongyan Wang()   

  1. CAS Key Laboratory of Systems Biology, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China
  • Received:2017-02-28 Revised:2017-03-22 Online:2017-07-20 Published:2017-06-28
  • Supported by:
    the National Natural Science Foundation of China(81571617, 31300723, 81671572, 31422018);the Strategic Priority Research Program of the Chinese Academy of Sciences Center for Excellence in Molecular Cell Science(XDB19000000);the Ministry of Science and Technology of China(2016YFD0500207, 2016YFC0902200)

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摘要：

Hippo信号通路通过一系列激酶级联反应,实现对细胞增殖、器官大小以及组织再生等方面的调控。其中,MST1/2是核心激酶Hippo蛋白在哺乳动物中的同源物,对于下游信号通路的激活至关重要。此外,MST1/2在细胞分化、形态和细胞骨架重排等方面也发挥重要作用。近期多项研究工作指出,MST1/2参与调控免疫T细胞的粘附、迁移、归巢和抑制性Treg细胞的成熟与功能,以及心肌细胞自噬等过程。有趣的是,这一功能是不依赖经典的Hippo信号通路的,被称为“非经典Hippo信号通路”。最新的研究结果揭示了MST1/2通过非经典Hippo信号通路调控先天免疫巨噬细胞对病原菌或病毒的免疫应答,包括巨噬细胞的吞噬、细胞因子(炎症因子、趋化因子、Ⅰ型干扰素等)和线粒体活性氧的产生,从而在机体抵抗细菌病毒感染、炎症相关癌症、动脉粥样硬化等疾病中发挥重要功能。本文对MST1/2调控先天免疫功能、相关分子机制和疾病进行了总结和讨论。

关键词: Hippo信号通路, MST1/2, 先天免疫, 巨噬细胞, 炎症相关疾病

Abstract:

The Hippo signaling pathway regulates cell proliferation, organ size and tissue regeneration through a series of kinase cascades. MST1/2 is the mammalian orthologue of the core kinase Hippo, which is crucial for the activation of downstream signaling. Additionally, MST1/2 has been reported to play important roles in cell differentiation, morphology and cytoskeleton reorganization. Recent evidence suggests that MST1/2 is involved in the regulation of T cell adhesion, migration, homing and Treg cell maturation and functions. Interestingly, these processes are not dependent on the canonical, but a non-canonical Hippo signaling pathway. More recent studies have revealed that MST1/2 mediates the innate immune response against pathogens or viruses, especially on macrophage phagocytosis as well as cytokines and ROS production. MST1/2 is associated with various diseases, such as bacterial or viral infection, inflammation-related cancer, and atherosclerosis. In this review, we summarize recent findings on the functions of MST1/2 in the innate immune response and inflammation-related diseases.

Key words: Hippo signaling pathway, MST1/2, innate immune, macrophage, inflammation-related disease