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

• Published in: iScience Vol. 24; no. 12; p. 103473
• Main Authors: Kanoh, Hirotaka, Iwashita, Shinzo, Kuraishi, Takayuki, Goto, Akira, Fuse, Naoyuki, Ueno, Haruna, Nimura, Mariko, Oyama, Tomohito, Tang, Chang, Watanabe, Ryo, Hori, Aki, Momiuchi, Yoshiki, Ishikawa, Hiroki, Suzuki, Hiroaki, Nabe, Kumiko, Takagaki, Takeshi, Fukuzaki, Masataka, Tong, Li-Li, Yamada, Sinya, Oshima, Yoshiteru, Aigaki, Toshiro, Dow, Julian A.T., Davies, Shireen-Anne, Kurata, Shoichiro
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 17-12-2021; Elsevier
• Subjects: Biological sciences; Genomics; Immune response; Genomics; Biological sciences; Immune response
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2021.103473

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.
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•Drosophila NF-κB signaling is activated by Gyc76C in parallel with the Toll receptor•Gyc76C modulates NF-κB signaling through downstream Toll receptor components•In Drosophila, 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 PP2A
Biological sciences; Immune response; Genomics