ID | 55298 |
フルテキストURL | |
著者 |
Sakaguchi, Masakiyo
Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Murata, Hitoshi
Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Kaken ID
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Aoyama, Yumi
Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Hibino, Toshihiko
Shiseido Research Center, Advanced Science Research
Widya Putranto, Endy
Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Winarsa Ruma, I. Made
Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Inoue, Yusuke
Faculty of Science and Technology, Division of Molecular Science, Gunma University
Sakaguchi, Yoshihiko
Interdisciplinary Research Organization, University of Miyazaki
Yamamoto, Ken-ichi
Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Kinoshita, Rie
Department of Biotechnology, Division of Chemistry and Biochemistry, Graduate School of Natural Science and Technology, Okayama University
Futami, Junichiro
Department of Biotechnology, Division of Chemistry and Biochemistry, Graduate School of Natural Science and Technology, Okayama University
Kataoka, Ken
Department of Life Science, Faculty of Science, Okayama University of Science
Iwatsuki, Keiji
Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Huh, Nam-ho
Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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抄録 | The receptor for advanced glycation end products (RAGE) is involved in the pathogenesis of many inflammatory, degenerative, and hyperproliferative diseases, including cancer. Previously, we revealed mechanisms of downstream signaling from ligand-activated RAGE, which recruits TIRAP/MyD88. Here, we showed that DNAX-activating protein 10 (DAP10), a transmembrane adaptor protein, also binds to RAGE. By artificial oligomerization of RAGE alone or RAGE-DAP10, we found that RAGE-DAP10 heterodimer formation resulted in a marked enhancement of Akt activation, whereas homomultimeric interaction of RAGE led to activation of caspase 8. Normal human epidermal keratinocytes exposed to S100A8/A9, a ligand for RAGE, at a nanomolar concentration mimicked the pro-survival response of RAGE-DAP10 interaction, although at a micromolar concentration, the cells mimicked the pro-apoptotic response of RAGE-RAGE. In transformed epithelial cell lines, A431 and HaCaT, in which endogenous DAP10 was overexpressed, and S100A8/A9, even at a micromolar concentration, led to cell growth and survival due to RAGE-DAP10 interaction. Functional blocking of DAP10 in the cell lines abrogated the Akt phosphorylation from S100A8/A9-activated RAGE, eventually leading to an increase in apoptosis. Finally, S100A8/A9, RAGE, and DAP10 were overexpressed in the psoriatic epidermis. Our findings indicate that the functional interaction between RAGE and DAP10 coordinately regulates S100A8/A9-mediated survival and/or apoptotic response of keratinocytes.
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キーワード | Cancer
Cell Biology
Keratinocyte
Psoriasis
Receptor for Advanced Glycation End Products (RAGE)
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備考 | 学位審査副論文
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発行日 | 2014-08
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出版物タイトル |
Journal of Biological Chemistry
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巻 | 289巻
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号 | 34号
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出版者 | American Society for Biochemistry and Molecular
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開始ページ | 23389
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終了ページ | 23402
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ISSN | 0021-9258
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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 | https://creativecommons.org/licenses/by-nc-nd/4.0/deed.ja
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論文のバージョン | publisher
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PubMed ID | |
DOI | |
Web of Science KeyUT | |
関連URL | https://doi.org/10.1074/jbc.M114.573071
http://ousar.lib.okayama-u.ac.jp/54281
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