Research ArticleImmunology

STING Specifies IRF3 Phosphorylation by TBK1 in the Cytosolic DNA Signaling Pathway

Science Signaling  06 Mar 2012:
Vol. 5, Issue 214, pp. ra20
DOI: 10.1126/scisignal.2002521

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Right Place and Right Context

As part of the innate immune response, various pattern recognition receptors, such as Toll-like receptor 3 (TLR3) and TLR4, activate the kinase TBK1, which phosphorylates the transcription factor IRF3, leading to the production of type I interferons (IFNs). Tanaka and Chen used an in vitro reconstitution system to investigate the mechanism by which TBK1-mediated IRF3 activation occurs in response to the presence of cytosolic DNA from viruses or bacteria, a response that depends on the adaptor protein STING (see the Perspective by Bowie). Cytosolic DNA triggered the sequential recruitment of TBK1 and IRF3 to STING, which acted as a scaffold upon which TBK1 phosphorylated both STING and IRF3. Given that not all pattern recognition receptors that stimulate TBK1 lead to IRF3 activation, the authors suggest that STING specifies the activation of IRF3 by a subset of receptors that activate both TBK1 and STING—and that other adaptor proteins may fulfill similar roles in other innate immune pathways.