Identification of tyrosine-9 of MAVS as critical target for inducible phosphorylation that determines activation

PLoS One. 2012;7(7):e41687. doi: 10.1371/journal.pone.0041687. Epub 2012 Jul 26.


Background: Innate immunity to viruses involves receptors such as RIG-I, which senses viral RNA and triggers an IFN-β signaling pathway involving the outer mitochondrial membrane protein MAVS. However, the functional status of MAVS phosphorylation remains elusive.

Methodology/principal findings: Here we demonstrate for the first time that MAVS undergoes extensive tyrosine phosphorylation upon viral infection, indicating that MAVS phosphorylation might play an important role in MAVS function. A tyrosine-scanning mutational analysis revealed that MAVS tyrosine-9 (Y9) is a phosphorylation site that is required for IFN-β signaling. Indeed, MAVS Y9F mutation severely impaired TRAF3/TRAF6 recruitment and displayed decreased tyrosine phosphorylation in response to VSV infection compared to wild type MAVS. Functionally, MAVS Y9 phosphorylation contributed to MAVS antiviral function without interfering with its apoptosis property.

Conclusions/significance: These experiments identify a novel residue of MAVS that is crucially involved in the recruitment of TRAF3/TRAF6 and in downstream propagation of MAVS signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / chemistry*
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Apoptosis
  • Cell Line
  • Humans
  • Immunity, Innate
  • Mice
  • Phosphorylation
  • Signal Transduction
  • TNF Receptor-Associated Factor 3 / metabolism
  • TNF Receptor-Associated Factor 6 / metabolism
  • Tyrosine / metabolism*
  • Vesiculovirus / physiology


  • Adaptor Proteins, Signal Transducing
  • IPS-1 protein, mouse
  • TNF Receptor-Associated Factor 3
  • TNF Receptor-Associated Factor 6
  • Tyrosine

Grants and funding

This work was supported in part by 973 grant 2012CB518900 and National Science Funding Committe(NSFC) Grant 31170029. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.