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

Siqi Liu, Xin Cai, Jiaxi Wu, Qian Cong, Xiang Chen, Tuo Li, Fenghe Du, Junyao Ren, You Tong Wu, Nick V. Grishin, Zhijian J. Chen

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446 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numberaaa2630
JournalScience
Volume347
Issue number6227
DOIs
StatePublished - Mar 13 2015

ASJC Scopus subject areas

  • General

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    Liu, S., Cai, X., Wu, J., Cong, Q., Chen, X., Li, T., Du, F., Ren, J., Wu, Y. T., Grishin, N. V., & Chen, Z. J. (2015). Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF induces IRF3 activation. Science, 347(6227), [aaa2630]. https://doi.org/10.1126/science.aaa2630