Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF induces IRF3 activation.
Science
; 347(6227): aaa2630, 2015 Mar 13.
Article
in En
| MEDLINE
| ID: mdl-25636800
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Adaptor Proteins, Vesicular Transport
/
Adaptor Proteins, Signal Transducing
/
Interferon Regulatory Factor-3
/
Membrane Proteins
Limits:
Animals
/
Humans
Language:
En
Journal:
Science
Year:
2015
Document type:
Article
Affiliation country:
United States