Cell 2011 Oct;147(2):436-46. [IF:32.401]
Activation of STAT6 by STING Is Critical for Antiviral Innate Immunity.
Chen H , Sun H , You F , Sun W , Zhou X , Chen L , Yang J , Wang Y , Tang H , Guan Y , Xia W , Gu J , Ishikawa H , Gutman D , Barber G , Qin Z , Jiang Z .
State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China; Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, School of Life Sciences, Peking University, Beijing, China.
北京大学生命科学院植物基因与蛋白研究重点实验室，细胞增殖与分化教育部重点实验室
Abstract
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.
