title: Activation of STAT6 by STING is critical for antiviral innate immunity.
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.
authors: State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China.
authors: Huihui
authors: H
authors: Chen
authors: Hui
authors: H
authors: Sun
authors: Fuping
authors: F
authors: You
authors: Wenxiang
authors: W
authors: Sun
authors: Xiang
authors: X
authors: Zhou
authors: Lu
authors: L
authors: Chen
authors: Jing
authors: J
authors: Yang
authors: Yutao
authors: Y
authors: Wang
authors: Hong
authors: H
authors: Tang
authors: Yukun
authors: Y
authors: Guan
authors: Weiwei
authors: W
authors: Xia
authors: Jun
authors: J
authors: Gu
authors: Hiroki
authors: H
authors: Ishikawa
authors: Delia
authors: D
authors: Gutman
authors: Glen
authors: G
authors: Barber
authors: Zhihai
authors: Z
authors: Qin
authors: Zhengfan
authors: Z
authors: Jiang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D007113:Immunity, Innate; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012327:RNA Virus Infections / Q000276:immunology*; D012328:RNA Viruses; D050800:STAT6 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D000099197:STING Protein
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D008565:Membrane Proteins; D017346:Protein Serine-Threonine Kinases; D050800:STAT6 Transcription Factor; C512612:MAVS protein, mouse; C494100:Stat6 protein, mouse; C530855:Sting1 protein, mouse; D000099197:STING Protein; C498588:Tbk1 protein, mouse