FullText URL K0005298_other1.pdf
Author 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|
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
File Version publisher
PubMed ID 25002577
DOI 10.1074/jbc.M114.573071
Web of Sience KeyUT 000341505000014
Related Url https://doi.org/10.1074/jbc.M114.573071 http://ousar.lib.okayama-u.ac.jp/54281