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

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: Her...

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Main Authors: Chaoyang Wen, Zhifeng Yan, Xiaoli Yang, Kai Guan, Changzhi Xu, Ting Song, Zirui Zheng, Wenjun Wang, Ying Wang, Man Zhao, Yanhong Zhang, Tao Xu, Jianping Dou, Jingmei Liu, Quanbin Xu, Xiang He, Congwen Wei, Hui Zhong
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3406013?pdf=render
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Summary: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.
ISSN:1932-6203