cGMP signaling pathway that modulates NF-κB activation in innate immune responses

The nuclear factor-kappa B (NF-kappa B) pathway is an evolutionarily conserved signaling pathway that plays a central role in immune responses and inflammation.Here, we show that Drosophila NF-kappa B 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-kappa B signaling through the downstream Tollreceptor components dMyd88,Pelle, Tube, and Dif/Dorsal (NF-kappa B). 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 in Drosophila. A membrane-bound cGK, PRKG2, also modulates NF-kappa B activation via PP2A in human cells, indicating that modulation of NF-kappa B activation in innate immunity by the cGMP signaling pathway is evolutionarily conserved.

Automated summary

The study demonstrates that the NF-kappa B signaling pathway in Drosophila is activated through a pathway parallel to the Toll receptor, involving the receptor-type guanylate cyclase Gyc76C. This pathway produces cGMP and modulates NF-kappa B signaling to combat bacterial infections. Furthermore, the modulation of NF-kappa B activation by the cGMP signaling pathway is evolutionarily conserved in both fruit flies and human cells.