ID | 61696 |
フルテキストURL | |
著者 |
Nakahara, Kengo
Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Hamada, Kyohei
Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Tsuchida, Tomoki
Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Takasugi, Nobumasa
Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Abiko, Yumi
Environmental Biology Laboratory, Faculty of Medicine, University of Tsukuba
Shien, Kazuhiko
Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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Toyooka, Shinichi
Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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Kumagai, Yoshito
Environmental Biology Laboratory, Faculty of Medicine, University of Tsukuba
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抄録 | The epidermal growth factor receptor (EGFR) is the most intensively investigated receptor tyrosine kinase. Several EGFR mutations and modifications have been shown to lead to abnormal self-activation, which plays a critical role in carcinogenesis. Environmental air pollutants, which are associated with cancer and respiratory diseases, can also activate EGFR. Specifically, the environmental electrophile 1,2-naphthoquinone (1,2-NQ), a component of diesel exhaust particles and particulate matter more generally, has previously been shown to impact EGFR signaling. However, the detailed mechanism of 1,2-NQ function is unknown. Here, we demonstrate that 1,2-NQ is a novel chemical activator of EGFR but not other EGFR family proteins. We found that 1,2-NQ forms a covalent bond, in a reaction referred to as N-arylation, with Lys80, which is in the ligand-binding domain. This modification activates the EGFR–Akt signaling pathway, which inhibits serum deprivation–induced cell death in a human lung adenocarcinoma cell line. Our study reveals a novel mode of EGFR pathway activation and suggests a link between abnormal EGFR activation and environmental pollutant–associated diseases such as cancer.
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キーワード | epidermal growth factor receptor
cell signaling
chemical modification
signal transduction
apoptosis
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発行日 | 2021-12-31
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出版物タイトル |
Journal of Biological Chemistry
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巻 | 296巻
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出版者 | Elsevier
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開始ページ | 100524
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ISSN | 00219258
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NCID | AA00251083
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資料タイプ |
学術雑誌論文
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言語 |
英語
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OAI-PMH Set |
岡山大学
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著作権者 | © 2021 The Authors.
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論文のバージョン | publisher
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PubMed ID | |
DOI | |
関連URL | isVersionOf https://doi.org/10.1016/j.jbc.2021.100524
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ライセンス | http://creativecommons.org/licenses/by/4.0/
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Citation | Nakahara K, Hamada K, Tsuchida T, Takasugi N, Abiko Y, Shien K, Toyooka S, Kumagai Y, Uehara T. Covalent N-arylation by the pollutant 1,2-naphthoquinone activates the EGF receptor. J Biol Chem. 2021 Mar 8;296:100524. doi: 10.1016/j.jbc.2021.100524. Epub ahead of print. PMID: 33705793; PMCID: PMC8050034.
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オープンアクセス(出版社) |
OA
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オープンアーカイブ(出版社) |
非OpenArchive
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