Bruton’s Tyrosine Kinase Phosphorylates DDX41 and Activates Its Binding of dsDNA and STING to Initiate Type 1 Interferon Response

• DOI: 10.1016/j.celrep.2015.01.039
• Publication Date: 2015-02-19T15:23:52Z
• Authors: Koon-Guan Lee; Susana Soo-Yeon Kim; Lin Kui; Dominic Chih-Chen...; Marjorie Mauduit; Pradeep Bist; Xuezhi Bi; Natasha Ann Pereira; Chengcheng Liu; Bindu Sukumaran; Laurent Rénia; Yoshiaki Ito; Kong-Peng Lam
• Keywords: Sting; IRF3; TANK-binding kinase 1

The innate immune system senses cytosolic dsDNA and bacterial cyclic dinucleotides initiates signaling via the adaptor STING to induce type 1 interferon (IFN) response. We demonstrate here that BTK-deficient cells have impaired IFN-β production TBK1/IRF3 activation when stimulated with agonists or infected pathogens activate signaling. BTK interacts DDX41 helicase. kinase SH3/SH2 interaction domains of bind, respectively, DEAD-box domain transmembrane region STING. phosphorylates DDX41, its activities are critical for STING-mediated production. show Tyr364 Tyr414 recognition AT-rich DNA binding STING, tandem mass spectrometry identifies as phosphorylation site. Modeling studies further indicate phospho-Tyr414 strengthens DDX41's Hence, plays a role in helicase