| First Author | Lee KG | Year | 2015 |
| Journal | Cell Rep | Volume | 10 |
| Issue | 7 | Pages | 1055-65 |
| PubMed ID | 25704810 | Mgi Jnum | J:324776 |
| Mgi Id | MGI:6837532 | Doi | 10.1016/j.celrep.2015.01.039 |
| Citation | Lee KG, et al. (2015) Bruton's tyrosine kinase phosphorylates DDX41 and activates its binding of dsDNA and STING to initiate type 1 interferon response. Cell Rep 10(7):1055-65 |
| abstractText | The innate immune system senses cytosolic dsDNA and bacterial cyclic dinucleotides and initiates signaling via the adaptor STING to induce type 1 interferon (IFN) response. We demonstrate here that BTK-deficient cells have impaired IFN-beta production and TBK1/IRF3 activation when stimulated with agonists or infected with pathogens that activate STING signaling. BTK interacts with STING and DDX41 helicase. The kinase and SH3/SH2 interaction domains of BTK bind, respectively, the DEAD-box domain of DDX41 and transmembrane region of STING. BTK phosphorylates DDX41, and its kinase activities are critical for STING-mediated IFN-beta production. We show that Tyr364 and Tyr414 of DDX41 are critical for its recognition of AT-rich DNA and binding to STING, and tandem mass spectrometry identifies Tyr414 as the BTK phosphorylation site. Modeling studies further indicate that phospho-Tyr414 strengthens DDX41's interaction with STING. Hence, BTK plays a critical role in the activation of DDX41 helicase and STING signaling. |
