Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF induces IRF3 activation

被引：1713

作者：

Liu, Siqi ^{[1
]}

Cai, Xin ^{[1
]}

Wu, Jiaxi ^{[1
]}

Cong, Qian ^{[2
,3
]}

Chen, Xiang ^{[1
,4
]}

Li, Tuo ^{[1
]}

Du, Fenghe ^{[1
,4
]}

Ren, Junyao ^{[1
]}

Wu, You-Tong ^{[1
]}

Grishin, Nick V. ^{[2
,3
,4
]}

Chen, Zhijian J. ^{[1
,4
]}

机构：

[1] Univ Texas SW Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA

[2] Univ Texas SW Med Ctr Dallas, Dept Biophys, Dallas, TX 75390 USA

[3] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA

[4] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA

来源：

SCIENCE | 2015年 / 347卷 / 6227期

关键词：

NF-KAPPA-B; CYCLIC GMP-AMP; CRYSTAL-STRUCTURE; RIG-I; NUCLEAR TRANSLOCATION; IKK-BETA; RECOGNITION; KINASE; SEQUENCE; COMPLEX;

D O I：

10.1126/science.aaa2630

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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.

引用

页码：1217 / U17

页数：15

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