Department of Molecular Genetics, Institute of Biomedical Science, Kansai Medical University, Hirakata, Japan.
Front Immunol. 2020 May 6;11:733. doi: 10.3389/fimmu.2020.00733. eCollection 2020.
The STE20-like serine/threonine kinases MST1 and MST2 (MST1/2) are mammalian homologs of Hippo in flies. MST1/2 regulate organ size by suppressing the transcription factor YAP, which promotes proliferation. MST1 is predominantly expressed in immune cells, where it plays distinct roles. Here, we review the functions of MST1/2 in immune cells, uncovered by a series of recent studies, and discuss the connection between MST1/2 function and immune responses. MST1/2 regulate lymphocyte development, trafficking, survival, and antigen recognition by naive T cells. MST1/2 also regulate the function of regulatory T cells and effector T cell differentiation, thus acting to balance immune activation and tolerance. Interestingly, MST1/2 elicit these functions not by the "canonical" Hippo pathway, but by the non-canonical Hippo pathway or alternative pathways. In these pathways, MST1/2 regulates cellular processes relating to immune response, such as chemotaxis, cell adhesion, immunological synapse, gene transcriptions. Recent advances in our understanding of the molecular mechanisms of these processes have revealed important roles of MST1/2 in regulating cytoskeleton remodeling, integrin activation, and vesicular transport in lymphocytes. We discuss the significance of the MST1/2 signaling in lymphocytes in the regulation of organelle dynamics.
STE20 样丝氨酸/苏氨酸激酶 MST1 和 MST2（MST1/2）是 Hippo 在果蝇中的哺乳动物同源物。MST1/2 通过抑制促进增殖的转录因子 YAP 来调节器官大小。MST1 主要在免疫细胞中表达，在那里发挥着不同的作用。在这里，我们回顾了最近一系列研究揭示的 MST1/2 在免疫细胞中的功能，并讨论了 MST1/2 功能与免疫反应之间的联系。MST1/2 调节淋巴细胞的发育、迁移、存活以及幼稚 T 细胞的抗原识别。MST1/2 还调节调节性 T 细胞和效应 T 细胞分化的功能，从而平衡免疫激活和耐受。有趣的是，MST1/2 通过“经典” Hippo 途径以外的非经典 Hippo 途径或替代途径发挥这些功能。在这些途径中，MST1/2 调节与免疫反应相关的细胞过程，如趋化性、细胞黏附、免疫突触、基因转录。我们对这些过程的分子机制的理解的最新进展揭示了 MST1/2 在调节淋巴细胞中细胞骨架重塑、整合素激活和囊泡运输中的重要作用。我们讨论了 MST1/2 在调节细胞器动态中的淋巴细胞信号转导的意义。
