Identification of tyrosine-9 of MAVS as critical target for inducible phosphorylation that determines activation.
Identification of tyrosine-9 of MAVS as critical target for inducible phosphorylation that determines activation.
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鉴定 MAVS 的酪氨酸 9 作为决定激活的诱导磷酸化的关键靶标
DOI：
10.1371/journal.pone.0041687
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Zhong H
中科院分区：
文献类型：
--
作者：
Wen C;Yan Z;Yang X;Guan K;Xu C;Song T;Zheng Z;Wang W;Wang Y;Zhao M;Zhang Y;Xu T;Dou J;Liu J;Xu Q;He X;Wei C;Zhong H
对病毒的免疫涉及RIG-I等受体，RIG-I感知病毒RNA并触发涉及线粒体外膜蛋白MAVS的IFN-β信号通路。然而，MAVS磷酸化的功能状态尚不清楚。本研究首次证明MAVS在病毒感染时发生广泛的酪氨酸磷酸化，表明MAVS磷酸化可能在MAVS功能中发挥重要作用。酪氨酸扫描突变分析显示，MAVS酪氨酸-9 （Y9）是IFN-β信号转导所必需的磷酸化位点。事实上，与野生型MAVS相比，MAVS Y9F突变严重损害了TRAF3/TRAF6的募集，并在VSV感染时显示酪氨酸磷酸化降低。在功能上，MAVS Y9磷酸化有助于MAVS的抗病毒功能，而不干扰其凋亡特性。这些实验发现了一个新的MAVS残基，它在TRAF3/TRAF6的募集和MAVS信号的下游传播中起着至关重要的作用。
BackgroundInnate 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 FindingsHere 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/SignificanceThese experiments identify a novel residue of MAVS that is crucially involved in the recruitment of TRAF3/TRAF6 and in downstream propagation of MAVS signaling.
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