Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF induces IRF3 activation
Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF induces IRF3 activation
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DOI：
10.1126/science.aaa2630
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发表时间：
2015-03-13
期刊：
影响因子：
56.9
通讯作者：
Chen, Zhijian J.
中科院分区：
文献类型：
--
作者：
Liu, Siqi;Cai, Xin;Chen, Zhijian J.
在病毒感染期间，衔接蛋白MAVS和STING分别从胞质核酸传感器RIG-I和cGAS传递信号，以诱导I型干扰素（IFN）和其他抗病毒分子。在这里，我们表明，MAVS和STING港口两个保守的丝氨酸和苏氨酸集群的激酶IKK和/或TBK 1在响应刺激磷酸化。然后，磷酸化的MAVS和STING结合到带正电荷的干扰素调节因子3（IRF 3）表面，从而募集IRF 3用于其磷酸化和被TBK 1激活。我们进一步表明，TRIF，Toll样受体信号转导中的衔接蛋白，通过类似的磷酸化依赖机制激活IRF 3。这些结果表明，先天衔接蛋白的磷酸化是一个必要的和保守的机制，选择性地招募IRF 3激活I型IFN途径。
During virus infection, the adaptor proteins MAVS and STING transduce signals from the cytosolic nucleic acid sensors RIG-I and cGAS, respectively, to induce type I interferons (IFNs) and other antiviral molecules. Here we show that MAVS and STING harbor two conserved serine and threonine clusters that are phosphorylated by the kinases IKK and/or TBK1 in response to stimulation. Phosphorylated MAVS and STING then bind to a positively charged surface of interferon regulatory factor 3 (IRF3) and thereby recruit IRF3 for its phosphorylation and activation by TBK1. We further show that TRIF, an adaptor protein in Toll-like receptor signaling, activates IRF3 through a similar phosphorylation-dependent mechanism. These results reveal that phosphorylation of innate adaptor proteins is an essential and conserved mechanism that selectively recruits IRF3 to activate the type I IFN pathway.