title: Identification of tyrosine-9 of MAVS as critical target for inducible phosphorylation that determines activation.
abstract: 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.
  
  
  RESULTS
  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
  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.
authors: Hainan Branch of Chinese PLA General Hospital Sanya City, Hainan, China.
authors: Chaoyang
authors: C
authors: Wen
authors: Zhifeng
authors: Z
authors: Yan
authors: Xiaoli
authors: X
authors: Yang
authors: Kai
authors: K
authors: Guan
authors: Changzhi
authors: C
authors: Xu
authors: Ting
authors: T
authors: Song
authors: Zirui
authors: Z
authors: Zheng
authors: Wenjun
authors: W
authors: Wang
authors: Ying
authors: Y
authors: Wang
authors: Man
authors: M
authors: Zhao
authors: Yanhong
authors: Y
authors: Zhang
authors: Tao
authors: T
authors: Xu
authors: Jianping
authors: J
authors: Dou
authors: Jingmei
authors: J
authors: Liu
authors: Quanbin
authors: Q
authors: Xu
authors: Xiang
authors: X
authors: He
authors: Congwen
authors: C
authors: Wei
authors: Hui
authors: H
authors: Zhong
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D006801:Humans; D007113:Immunity, Innate; D051379:Mice; D010766:Phosphorylation; D015398:Signal Transduction; D048008:TNF Receptor-Associated Factor 3 / Q000378:metabolism; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism*; D018116:Vesiculovirus / Q000502:physiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D048008:TNF Receptor-Associated Factor 3; D048029:TNF Receptor-Associated Factor 6; D014443:Tyrosine; C512612:MAVS protein, mouse