2021年
Covalent N-arylation by the pollutant 1,2-naphthoquinone activates the EGF receptor.
J. Biol. Chem.
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- 巻
- 296
- 号
- 開始ページ
- 100524
- 終了ページ
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1016/j.jbc.2021.100524
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.
- リンク情報
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- DOI
- https://doi.org/10.1016/j.jbc.2021.100524
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/33705793
- Scopus
- https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85104618413&origin=inward 本文へのリンクあり
- Scopus Citedby
- https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=85104618413&origin=inward
- ID情報
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- DOI : 10.1016/j.jbc.2021.100524
- ISSN : 0021-9258
- eISSN : 1083-351X
- PubMed ID : 33705793
- SCOPUS ID : 85104618413