Protein S-guanylation by the biological signal 8-nitroguanosine 3′,5′-cyclic monophosphate

Tomohiro Sawa, Mohammad Hasan Zaki, Tatsuya Okamoto, Teruo Akuta, Yoshiko Tokutomi, Shokei Kim-Mitsuyama, Hideshi Ihara, Akira Kobayashi, Masayuki Yamamoto, Shigemoto Fujii, Hirokazu Arimoto, Takaaki Akaike

Research output: Contribution to journalArticle

164 Citations (Scopus)

Abstract

The signaling pathway of nitric oxide (NO) depends mainly on guanosine 3′,5′-cyclic monophosphate (cGMP, 1). Here we report the formation and chemical biology of a nitrated derivative of cGMP, 8-nitroguanosine 3′,5′-cyclic monophosphate (8-nitro-cGMP, 2), in NO-mediated signal transduction. Immunocytochemistry demonstrated marked 8-nitro-cGMP production in various cultured cells in an NO-dependent manner. This finding was confirmed by HPLC plus electrochemical detection and tandem mass spectrometry. 8-Nitro-cGMP activated cGMP-dependent protein kinase and showed unique redox-active properties independent of cGMP activity. Formation of protein Cys-cGMP adducts by 8-nitro-cGMP was identified as a new post-translational modification, which we call protein S-guanylation. 8-Nitro-cGMP seems to regulate the redox-sensor signaling protein Keap1, via S-guanylation of the highly nucleophilic cysteine sulfhydryls of Keap1. This study reveals 8-nitro-cGMP to be a second messenger of NO and sheds light on new areas of the physiology and chemical biology of signal transduction by NO.

Original languageEnglish (US)
Pages (from-to)727-735
Number of pages9
JournalNature Chemical Biology
Volume3
Issue number11
DOIs
StatePublished - Nov 2007

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Protein S
Nitric Oxide
Oxidation-Reduction
Signal Transduction
Cyclic GMP-Dependent Protein Kinases
Guanosine
Second Messenger Systems
Post Translational Protein Processing
Tandem Mass Spectrometry
Cysteine
8-nitroguanosine 3',5'-cyclic monophosphate
8-nitroguanosine
Cultured Cells
Proteins
Immunohistochemistry
High Pressure Liquid Chromatography

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Protein S-guanylation by the biological signal 8-nitroguanosine 3′,5′-cyclic monophosphate. / Sawa, Tomohiro; Zaki, Mohammad Hasan; Okamoto, Tatsuya; Akuta, Teruo; Tokutomi, Yoshiko; Kim-Mitsuyama, Shokei; Ihara, Hideshi; Kobayashi, Akira; Yamamoto, Masayuki; Fujii, Shigemoto; Arimoto, Hirokazu; Akaike, Takaaki.

In: Nature Chemical Biology, Vol. 3, No. 11, 11.2007, p. 727-735.

Research output: Contribution to journalArticle

Sawa, T, Zaki, MH, Okamoto, T, Akuta, T, Tokutomi, Y, Kim-Mitsuyama, S, Ihara, H, Kobayashi, A, Yamamoto, M, Fujii, S, Arimoto, H & Akaike, T 2007, 'Protein S-guanylation by the biological signal 8-nitroguanosine 3′,5′-cyclic monophosphate', Nature Chemical Biology, vol. 3, no. 11, pp. 727-735. https://doi.org/10.1038/nchembio.2007.33
Sawa, Tomohiro ; Zaki, Mohammad Hasan ; Okamoto, Tatsuya ; Akuta, Teruo ; Tokutomi, Yoshiko ; Kim-Mitsuyama, Shokei ; Ihara, Hideshi ; Kobayashi, Akira ; Yamamoto, Masayuki ; Fujii, Shigemoto ; Arimoto, Hirokazu ; Akaike, Takaaki. / Protein S-guanylation by the biological signal 8-nitroguanosine 3′,5′-cyclic monophosphate. In: Nature Chemical Biology. 2007 ; Vol. 3, No. 11. pp. 727-735.
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