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

Journal volume & issue
Vol. 24, no. 12
p. 103473

Abstract

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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.

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