Activation of STAT6 by STING Is Critical for Antiviral Innate Immunity

被引：323

作者：

Chen, Huihui ^{[1
,2
]}

Sun, Hui ^{[1
,2
]}

You, Fuping ^{[1
,2
]}

Sun, Wenxiang ^{[1
,2
]}

Zhou, Xiang ^{[1
,2
]}

Chen, Lu ^{[1
,2
]}

Yang, Jing ^{[1
,2
]}

Wang, Yutao ^{[1
,2
]}

Tang, Hong ^{[1
,2
]}

Guan, Yukun ^{[1
,2
]}

Xia, Weiwei ^{[1
]}

Gu, Jun ^{[1
]}

Ishikawa, Hiroki ^{[4
,5
]}

Gutman, Delia ^{[4
,5
]}

Barber, Glen ^{[4
,5
]}

Qin, Zhihai ^{[6
]}

Jiang, Zhengfan ^{[1
,2
,3
]}

机构：

[1] Peking Univ, Sch Life Sci, State Key Lab Prot & Plant Gene Res, Beijing 100871, Peoples R China

[2] Peking Univ, Sch Life Sci, Key Lab Cell Proliferat & Differentiat, Minist Educ, Beijing 100871, Peoples R China

[3] Tsinghua Univ, Peking Univ, Joint Ctr Life Sci, Beijing 100084, Peoples R China

[4] Univ Miami, Sch Med, Dept Med, Miami, FL 33136 USA

[5] Univ Miami, Sch Med, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA

[6] Inst Biophys, State Key Lab Biomacromol, Beijing, Peoples R China

来源：

CELL | 2011年 / 147卷 / 02期

关键词：

NF-KAPPA-B; RIG-I; ADAPTER PROTEIN; CYTOSOLIC DNA; EXPRESSION; ALPHA; CELLS; INTERLEUKIN-4; RECOGNITION; RESPONSES;

D O I：

10.1016/j.cell.2011.09.022

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

STAT6 plays a prominent role in adaptive immunity by transducing signals from extracellular cytokines. We now show that STAT6 is required for innate immune signaling in response to virus infection. Viruses or cytoplasmic nucleic acids trigger STING (also named MITA/ERIS) to recruit STAT6 to the endoplasmic reticulum, leading to STAT6 phosphorylation on Ser(407) by TBK1 and Tyr(641), independent of JAKs. Phosphorylated STAT6 then dimerizes and translocates to the nucleus to induce specific target genes responsible for immune cell homing. Virus-induced STAT6 activation is detected in all cell-types tested, in contrast to the cell-type specific role of STAT6 in cytokine signaling, and Stat6(-/-) mice are susceptible to virus infection. Thus, STAT6 mediates immune signaling in response to both cytokines at the plasma membrane, and virus infection at the endoplasmic reticulum.

引用

页码：436 / 446

页数：11

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