STING, a transmembrane protein in the endoplasmic reticulum, interacts with various cytosolic DNA sensors to induce the production of interferon-β via a pathway dependent on the transcription factor IRF3. In Science Signaling, Tanaka and Chen show that STING acts as a scaffold that recruits IRF3. This interaction requires Ser366 and Leu374 in the conserved carboxy-terminal domain of STING. This domain also recruits and activates the kinase TBK1. TBK1 phosphorylates IRF3, which leads to its dimerization and translocation to the nucleus. Notably, although TBK1 is activated by many signaling pathways, such as Toll-like receptors, not all lead to IRF3 activation. In response to cytosolic duplex DNA, however, STING is needed to place IRF3 in proximity with TBK1, thereby activating IRF3-dependent responses to combat infection with double-stranded DNA viruses or intercellular bacteria.

Sci. Signal. 5, 214 ra20 (2012)