iScience (Dec 2021)
cGMP signaling pathway that modulates NF-κB activation in innate immune responses
- Hirotaka Kanoh,
- Shinzo Iwashita,
- Takayuki Kuraishi,
- Akira Goto,
- Naoyuki Fuse,
- Haruna Ueno,
- Mariko Nimura,
- Tomohito Oyama,
- Chang Tang,
- Ryo Watanabe,
- Aki Hori,
- Yoshiki Momiuchi,
- Hiroki Ishikawa,
- Hiroaki Suzuki,
- Kumiko Nabe,
- Takeshi Takagaki,
- Masataka Fukuzaki,
- Li-Li Tong,
- Sinya Yamada,
- Yoshiteru Oshima,
- Toshiro Aigaki,
- Julian A.T. Dow,
- Shireen-Anne Davies,
- Shoichiro Kurata
Affiliations
- Hirotaka Kanoh
- Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan
- Shinzo Iwashita
- Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan
- Takayuki Kuraishi
- Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan; PRESTO, Japan Science and Technology Agency, Tokyo, Japan
- Akira Goto
- Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan; Graduate School of Life Sciences, Tohoku University, Sendai 980-8578, Japan
- Naoyuki Fuse
- Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan
- Haruna Ueno
- Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan
- Mariko Nimura
- Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan
- Tomohito Oyama
- Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan
- Chang Tang
- Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan
- Ryo Watanabe
- Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan
- Aki Hori
- Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan
- Yoshiki Momiuchi
- Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan
- Hiroki Ishikawa
- Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan
- Hiroaki Suzuki
- Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan
- Kumiko Nabe
- Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan
- Takeshi Takagaki
- Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan
- Masataka Fukuzaki
- Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan
- Li-Li Tong
- Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan
- Sinya Yamada
- Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan
- Yoshiteru Oshima
- Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan
- Toshiro Aigaki
- Department of Biological Sciences, Tokyo Metropolitan University, Tokyo 192-0397, Japan
- Julian A.T. Dow
- Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK
- Shireen-Anne Davies
- Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK
- Shoichiro Kurata
- Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan; Corresponding author
- Journal volume & issue
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Vol. 24,
no. 12
p. 103473
Abstract
Summary: 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.
