STAT1信号通路概述.pdf

中国科技论文在线 STAT1 信号通路概述# 胡思哲，蒋海，刘鸿，齐宏妍，邵吉民** （浙江大学医学院病理学与病理生理学系，杭州 310058 ） 5 摘要：信号转导与转录激活子（STAT ）家族包括7 个成员：STAT1、STAT2、STAT3、STAT4、 STAT5A、STAT5B 以及 STAT6。STAT1 主要受IFN 的激活，调节许多参与细胞生长、分 化、凋亡及免疫的基因的表达。细胞因子可促进STAT1 酪氨酸及丝氨酸位点的磷酸化，入 核后形成同/异二聚体激活下游基因的表达。STAT1 的失活机制使得其调控下游基因有严格 10 的时间限制，赖氨酸乙酰化被认为是终止STAT1 的重要信号。本文就过去20 多年对STAT1 的研究进展进行概述，着重讲述STAT1 信号的激活与终止及其生物学功能等。 关键词：病理学与病理生理学；STAT1；激活；失活；免疫；癌症 中图分类号：R363.2+1 15 Signal Transduction Pathway of STAT1 Hu Sizhe, Jiang Hai, Liu Hong, Qi Hongyan, Shao Jimin (Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou 310058) Abstract: Signal transducer and activator of transcription (STAT) family consist of seven 20 members: STAT1, STAT2, STAT3, STAT4, STAT5A, STAT5B and STAT6. STAT1 is preferentially activated by interferon (IFN) and thereby regulates the gene expressions involved in cell growth, differentiation, apoptosis and immune response. Cytokine-induced tyrosine and serine phosphorylation facilitate STAT1 homo/hetero- dimerization, nuclear translocation and transactivation of downstream gene expression. The transcription of STAT1-targeted genes is 25 strictly regulated in a time limited manner, while the inactivation of STAT1 is likely mediated by acetylation. Here we summarized the research progress of STAT1 signaling activation/termination and their biological functions in the past 20 years. Key words: pathology and pathophysiology; STAT1; activation; inactivation; immunity; cancer 30 0 引言 信号转导与转录激活子(STAT)通路在所有脊椎动物和一些早期的后生动物中是高度保 守的，它能够通过简单而直接的方式把许多细胞因子的信号从细胞膜受体传导到细胞核内，