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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
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
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.
キーワード
Cancer
Cell Biology
Keratinocyte
Psoriasis
Receptor for Advanced Glycation End Products (RAGE)
備考
学位審査副論文
発行日
2014-08
出版物タイトル
Journal of Biological Chemistry
289巻
34号
出版者
American Society for Biochemistry and Molecular
開始ページ
23389
終了ページ
23402
ISSN
0021-9258
NCID
AA00251083
資料タイプ
学術雑誌論文
言語
English
OAI-PMH Set
岡山大学
著作権者
https://creativecommons.org/licenses/by-nc-nd/4.0/deed.ja
論文のバージョン
publisher
PubMed ID
DOI
Web of Sience KeyUT
関連URL
https://doi.org/10.1074/jbc.M114.573071
http://ousar.lib.okayama-u.ac.jp/54281