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ID 55298
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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
Abstract
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.
Keywords
Cancer
Cell Biology
Keratinocyte
Psoriasis
Receptor for Advanced Glycation End Products (RAGE)
Note
学位審査副論文
Published Date
2014-08
Publication Title
Journal of Biological Chemistry
Volume
volume289
Issue
issue34
Publisher
American Society for Biochemistry and Molecular
Start Page
23389
End Page
23402
ISSN
0021-9258
NCID
AA00251083
Content Type
Journal Article
language
英語
OAI-PMH Set
岡山大学
Copyright Holders
https://creativecommons.org/licenses/by-nc-nd/4.0/deed.ja
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DOI
Web of Sience KeyUT
Related Url
https://doi.org/10.1074/jbc.M114.573071
http://ousar.lib.okayama-u.ac.jp/54281