Kanoh, H., Iwashita, S., Kuraishi, T., Goto, A., Fuse, N., Ueno, H., Nimura, M., Oyama, T., Tang, C., Watanabe, R., Hori, A., Momiuchi, Y., Ishikawa, H., Suzuki, H., Nabe, K., Takagaki, T., Fukuzaki, M., Tong, L.L., Yamada, S., Oshima, Y., Aigaki, T., Dow, J.A.T., Davies, S.A., Kurata, S. (2021). cGMP signaling pathway that modulates NF-κB activation in innate immune responses.  iScience 24(12): 103473.

FBrf0252339

Research paper

The 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 that Drosophila NF-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 in Drosophila. 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.

PMC8710550 (PMC) (EuropePMC)