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 OshimaToshiro Aigaki, Julian A.T. Dow, Shireen Anne Davies, Shoichiro Kurata

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number103473
JournaliScience
Volume24
Issue number12
DOIs
Publication statusPublished - 2021 Dec 17

Keywords

  • Biological sciences
  • Genomics
  • Immune response

ASJC Scopus subject areas

  • General

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