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7143824 
Journal Article 
Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF induces IRF3 activation 
Liu, S; Cai, X; Wu, J; Cong, Q; Chen, X; Li, T; Du, F; Ren, J; Wu, YT; Grishin, NV; Chen, ZJ; , 
2015 
1 
Science
ISSN: 0036-8075
EISSN: 1095-9203 
English 
25636800 
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.