摘要：SummaryThe nuclear factor-kappa B (NF-κB) pathway is an evolutionarily conserved signaling pathway that plays a central role in immune responses and inflammation. Here, we show thatDrosophilaNF-κB signaling is activated via a pathway in parallel with the Toll receptor by receptor-type guanylate cyclase, Gyc76C. Gyc76C produces cyclic guanosine monophosphate (cGMP) and modulates NF-κB signaling through the downstream Tollreceptor components dMyd88, Pelle, Tube, and Dif/Dorsal (NF-κB). The cGMP signaling pathway comprises a membrane-localized cGMP-dependent protein kinase (cGK) called DG2 and protein phosphatase 2A (PP2A) and is crucial for host survival against Gram-positive bacterial infections inDrosophila. A membrane-bound cGK, PRKG2, also modulates NF-κB activation via PP2A in human cells, indicating that modulation of NF-κB activation in innate immunity by the cGMP signaling pathway is evolutionarily conserved.Graphical abstractDisplay OmittedHighlights•DrosophilaNF-κB signaling is activated by Gyc76C in parallel with the Toll receptor•Gyc76C modulates NF-κB signaling through downstream Toll receptor components•InDrosophila, the pathway comprises a cGMP-dependent protein kinase (cGK) and PP2A•In human cells, a membrane-bound cGK, PRKG2, also modulates NF-κB signaling via PP2ABiological sciences; Immune response; Genomics
