刺
内部收益率3
干扰素基因刺激剂
信号转导衔接蛋白
坦克结合激酶1
干扰素调节因子
胞浆
细胞生物学
磷酸化
信号转导
生物
转录因子
化学
蛋白激酶A
生物化学
基因
酶
工程类
航空航天工程
丝裂原活化蛋白激酶激酶
作者
Yasuo Tanaka,Zhijian J. Chen
出处
期刊:Science Signaling
[American Association for the Advancement of Science (AAAS)]
日期:2012-03-06
卷期号:5 (214)
被引量:976
标识
DOI:10.1126/scisignal.2002521
摘要
Cytosolic double-stranded DNA (dsDNA) stimulates the production of type I interferon (IFN) through the endoplasmic reticulum (ER)-resident adaptor protein STING (stimulator of IFN genes), which activates the transcription factor interferon regulatory factor 3 (IRF3); however, how STING activates IRF3 is unclear. Here, we showed that STING stimulates phosphorylation of IRF3 by the kinase TBK1 (TANK-binding kinase 1) in an in vitro reconstitution system. With this system, we identified a carboxyl-terminal region of STING that was both necessary and sufficient to activate TBK1 and stimulate the phosphorylation of IRF3. We also found that STING interacted with both TBK1 and IRF3 and that mutations in STING that selectively disrupted its binding to IRF3 abrogated phosphorylation of IRF3 without impairing the activation of TBK1. These results suggest that STING functions as a scaffold protein to specify and promote the phosphorylation of IRF3 by TBK1. This scaffolding function of STING (and possibly of other adaptor proteins) may explain why IRF3 is activated in only a subset of signaling pathways that activate TBK1.
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