@article{febaa4debf9d4585964da489f5bb402a,
title = "cGMP signaling pathway that modulates NF-κB activation in innate immune responses",
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.",
keywords = "Biological sciences, Genomics, Immune response",
author = "Hirotaka Kanoh and Shinzo Iwashita and Takayuki Kuraishi and Akira Goto and Naoyuki Fuse and Haruna Ueno and Mariko Nimura and Tomohito Oyama and Chang Tang and Ryo Watanabe and Aki Hori and Yoshiki Momiuchi and Hiroki Ishikawa and Hiroaki Suzuki and Kumiko Nabe and Takeshi Takagaki and Masataka Fukuzaki and Tong, {Li Li} and Sinya Yamada and Yoshiteru Oshima and Toshiro Aigaki and Dow, {Julian A.T.} and Davies, {Shireen Anne} and Shoichiro Kurata",
note = "Funding Information: We thank K.V. Anderson, D. Ferrandon, J.A. Hoffmann, D. Hultmark, J.L. Imler, Y.T. Ip, A.L. Kolodkin, B. Lemaitre, T. Muta, N. Perrimon, J-M. Reichhart, J. Royet, the Bloomington Stock Center, the Drosophila Genomics Resource Center at Indiana University, the Drosophila Genetic Resource Center at the Kyoto Institute of Technology, the Drosophila RNAi Screening Center, the Genetic Strain Research Center of National Institute of Genetics, and the Vienna Drosophila RNAi Center for fly stocks and materials; T. Kaisho, K. Miyake, T. Muta, and Y. Ogawa for discussions; and J. Alfred for editing the manuscript. This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT 19H03365, 16H05084, 24390014, 21117005, 21117001, and 14657577); the Japan Society for the Promotion of Science (JSPS); Japan Science and Technology Agency (JST); the Program for the Promotion of Basic Research Activities for Innovative Biosciences (PROBRAIN); the Strategic International Cooperative program from Japan Science and Technology Agency; the National Institutes of Health (AI07495); the Takeda Science Foundation; the Mitsubishi Foundation; the Astellas Foundation for Research on Metabolic Disorders; the Uehara Memorial Foundation; the Naito Foundation; a Global COE Research Grant (Tohoku University Ecosystem Adaptability); and Biotechnological and Biological Research Sciences Council (UK) grant number BB/E011438/1 to SD and JATD. H.K, S.I. T.K. A.G. and N.F. performed many of the experiments in this study with input from S.K.; H.U. and R.W. performed the ModSP experiments; A.H. Y.M. and L.L.T. performed the larval infection experiments; H.I. performed the PRKG2 analyses; K.N. performed the gain-of-function screen and identified CG3216; T.T. performed the gain-of-function screen; M.N. and T.A. performed the GNBP-1 and Psh experiments; T.A. and H.U. performed the Gyc76C ligand assay; C.T. performed the C. glabrata infection experiments; S.Y. performed the okadaic acid experiments; H.S and M.F. performed the epistatic analyses; Y.O. promoted this study; T.A. provided GS lines for the gain-of-screen; S-A.D. and J.A.T.D. designed the cGMP studies; and S.K. provided overall coordination with respect to conception, design, and supervision of the study and wrote the manuscript with comments from co-authors. H.K. S.I. T.K. A.G. and N.F. contributed equally to the study. All authors discussed the results. The authors declare no competing interests. Funding Information: We thank K.V. Anderson, D. Ferrandon, J.A. Hoffmann, D. Hultmark, J.L. Imler, Y.T. Ip, A.L. Kolodkin, B. Lemaitre, T. Muta, N. Perrimon, J-M. Reichhart, J. Royet, the Bloomington Stock Center, the Drosophila Genomics Resource Center at Indiana University, the Drosophila Genetic Resource Center at the Kyoto Institute of Technology, the Drosophila RNAi Screening Center, the Genetic Strain Research Center of National Institute of Genetics, and the Vienna Drosophila RNAi Center for fly stocks and materials; T. Kaisho, K. Miyake, T. Muta, and Y. Ogawa for discussions; and J. Alfred for editing the manuscript. This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT 19H03365 , 16H05084 , 24390014 , 21117005 , 21117001 , and 14657577 ); the Japan Society for the Promotion of Science (JSPS); Japan Science and Technology Agency (JST); the Program for the Promotion of Basic Research Activities for Innovative Biosciences (PROBRAIN); the Strategic International Cooperative program from Japan Science and Technology Agency ; the National Institutes of Health ( AI07495 ); the Takeda Science Foundation ; the Mitsubishi Foundation ; the Astellas Foundation for Research on Metabolic Disorders ; the Uehara Memorial Foundation ; the Naito Foundation ; a Global COE Research Grant (Tohoku University Ecosystem Adaptability); and Biotechnological and Biological Research Sciences Council (UK) grant number BB/E011438/1 to SD and JATD. Publisher Copyright: {\textcopyright} 2021 The Author(s)",
year = "2021",
month = dec,
day = "17",
doi = "10.1016/j.isci.2021.103473",
language = "English",
volume = "24",
journal = "iScience",
issn = "2589-0042",
publisher = "Elsevier Inc.",
number = "12",
}