{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T05:20:34Z","timestamp":1791955234844,"version":"4.3.4"},"reference-count":113,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2020,11,19]],"date-time":"2020-11-19T00:00:00Z","timestamp":1605744000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JSPS KAKENHI","award":["No. 18K11083"],"award-info":[{"award-number":["No. 18K11083"]}]},{"name":"JSPS KAKENHI","award":["No. 15K18994"],"award-info":[{"award-number":["No. 15K18994"]}]},{"name":"JSPS KAKENHI","award":["No. 26111008"],"award-info":[{"award-number":["No. 26111008"]}]},{"name":"JSPS KAKENH","award":["No. 18K14853"],"award-info":[{"award-number":["No. 18K14853"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Reactive oxygen species (ROS) are not only harmful to cell survival but also essential to cell signaling through cysteine-based redox switches. In fact, ROS triggers the potential activation of mitogen-activated protein kinases (MAPKs). The 90 kDa ribosomal S6 kinase 1 (RSK1), one of the downstream mediators of the MAPK pathway, is implicated in various cellular processes through phosphorylating different substrates. As such, RSK1 associates with and phosphorylates neuronal nitric oxide (NO) synthase (nNOS) at Ser847, leading to a decrease in NO generation. In addition, the RSK1 activity is sensitive to inhibition by reversible cysteine-based redox modification of its Cys223 during oxidative stress. Aside from oxidative stress, nitrosative stress also contributes to cysteine-based redox modification. Thus, the protein kinases such as Ca2+\/calmodulin (CaM)-dependent protein kinase I (CaMKI) and II (CaMKII) that phosphorylate nNOS could be potentially regulated by cysteine-based redox modification. In this review, we focus on the role of post-translational modifications in regulating nNOS and nNOS-phosphorylating protein kinases and communication among themselves.<\/jats:p>","DOI":"10.3390\/ijms21228750","type":"journal-article","created":{"date-parts":[[2020,11,19]],"date-time":"2020-11-19T10:46:26Z","timestamp":1605782786000},"page":"8750","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":107,"title":["Oxidative Stress Orchestrates MAPK and Nitric-Oxide Synthase Signal"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6691-2569","authenticated-orcid":false,"given":"Tsuyoshi","family":"Takata","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Showa Pharmaceutical University, Machida, Tokyo 194-8543, Japan"},{"name":"Department of Environmental Health Sciences and Molecular Toxicology, Graduate School of Medicine, Tohoku University, Miyagi 980-8575, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2034-2799","authenticated-orcid":false,"given":"Shoma","family":"Araki","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Showa Pharmaceutical University, Machida, Tokyo 194-8543, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1526-3351","authenticated-orcid":false,"given":"Yukihiro","family":"Tsuchiya","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Showa Pharmaceutical University, Machida, Tokyo 194-8543, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2232-0091","authenticated-orcid":false,"given":"Yasuo","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Showa Pharmaceutical University, Machida, Tokyo 194-8543, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1385\/MB:31:2:151","article-title":"The ERK Cascade: A Prototype of MAPK Signaling","volume":"31","author":"Rubinfeld","year":"2005","journal-title":"Mol. 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