核酸免疫识别的机制和功能及酪氨酸磷酸化修饰调控  

Advancements in tyrosine kinase-mediated regulation of innate nucleic acid sensing

作　　者：刘盛铎 徐平龙 LIU Shengduo;XU Pinglong(Institute of Intelligent Medicine,Hangzhou GlobalScientific and Technological Innovation Center,Zhejiang University,Hangzhou 311200,China;Life Sciences Institute,Zhejiang University,Hangzhou 310058,China;Key Laboratory of Biosystems Homeostasis and Protection,Ministry of Education,ZhejiangProvincial Key Laboratory for Cancer Molecular Cell Biology,Zhejiang University,Hangzhou 310058,China;Cancer Center,Zhejiang University,Hangzhou 310058,China)

机构地区：[1]浙江大学杭州国际科创中心智能医药研究所,浙江杭州311200 [2]浙江大学生命科学研究院,浙江杭州310058 [3]浙江大学生命系统稳态与保护教育部重点实验室、浙江省癌症分子细胞生物学重点实验室,浙江杭州310058 [4]浙江大学癌症研究院,浙江杭州310058

出　　处：《浙江大学学报（医学版）》2024年第1期35-46,共12页Journal of Zhejiang University(Medical Sciences)

基　　金：国家自然科学基金(82001746,31830052);浙江省自然科学基金(LY24C080001)。

摘　　要：核酸天然免疫识别是一种普遍存在且高度保守的免疫应答机制,负责监测和响应病原体入侵或组织损伤,进而在宿主防御、自身免疫反应、细胞命运决定以及肿瘤发生发展中发挥关键作用。酪氨酸磷酸化作为一类主要的蛋白质翻译后修饰机制,在核酸识别通路中发挥重要调控功能。其中,介导核酸免疫识别通路的核心成员环鸟苷酸-腺苷酸合成酶(cGAS)、干扰素基因刺激因子(STING)以及TANK结合激酶1(TBK1)等蛋白均受到酪氨酸磷酸化修饰引发的活性调控,进而影响生理或病理条件下宿主的抗病毒防御和抗肿瘤免疫能力。本文综述了酪氨酸激酶和酪氨酸磷酸化修饰在核酸免疫识别中的调控作用及研究现状,讨论了靶向酪氨酸磷酸化在抗肿瘤免疫中的功能和潜在应用,以期为理解并拓展全新的抗肿瘤手段提供思路。Innate nucleic acid sensing is a ubiquitous and highly conserved immunological process,which is pivotal for monitoring and responding to pathogenic invasion and cellular damage,and central to host defense,autoimmunity,cell fate determination and tumorigenesis.Tyrosine phosphorylation,a major type of posttranslational modification,plays a critical regulatory role in innate immune sensing pathway.Core members of nucleic acid sensing signaling pathway,such as cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS),stimulator of interferon genes(STING),and TANK binding kinase 1(TBK1),are all subject to activity regulation triggered by tyrosine phosphorylation,thereby affecting the host antiviral defense and anti-tumor immunity under physiological or pathological conditions.This review summarizes the recent advances in research on tyrosine kinases and tyrosine phosphorylation in regulation of nucleic acid sensing.The function and potential applications of targeting tyrosine phosphorylation in anti-tumor immunity is disussed to provide insights for understanding and expanding new anti-tumor strategies.

关 键 词：天然免疫 肿瘤免疫 酪氨酸磷酸化 酪氨酸激酶 信号转导 蛋白质修饰 环鸟苷酸-腺苷酸合成酶-干扰素基因刺激因子 综述 

分 类 号：R394[医药卫生—医学遗传学]