フルテキストURL K0005298_other1.pdf
著者 Sakaguchi, Masakiyo| Murata, Hitoshi| Aoyama, Yumi| Hibino, Toshihiko| Widya Putranto, Endy| Winarsa Ruma, I. Made| Inoue, Yusuke| Sakaguchi, Yoshihiko| Yamamoto, Ken-ichi| Kinoshita, Rie| Futami, Junichiro| Kataoka, Ken| Iwatsuki, Keiji| Huh, Nam-ho|
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 25002577
DOI 10.1074/jbc.M114.573071
Web of Sience KeyUT 000341505000014
関連URL https://doi.org/10.1074/jbc.M114.573071 http://ousar.lib.okayama-u.ac.jp/54281