title: DNAX-activating protein 10 (DAP10) membrane adaptor associates with receptor for advanced glycation end products (RAGE) and modulates the RAGE-triggered signaling pathway in human keratinocytes.
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.
authors.affiliation: From the Departments of Cell Biology and masa-s@md.okayama-u.ac.jp.
authors.forename: Masakiyo
authors.initials: M
authors.lastname: Sakaguchi
authors.affiliation: From the Departments of Cell Biology and.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Murata
authors.affiliation: Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikatacho, Kita-ku, Okayama 700-8558.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Aoyama
authors.affiliation: the Shiseido Research Center, Advanced Science Research, 2-2-1 Hayabuchi, Tsuzuki-ku, Yokohama 224-8558.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Hibino
authors.affiliation: From the Departments of Cell Biology and.
authors.forename: Endy Widya
authors.initials: EW
authors.lastname: Putranto
authors.affiliation: From the Departments of Cell Biology and.
authors.forename: I Made Winarsa
authors.initials: IM
authors.lastname: Ruma
authors.affiliation: the Faculty of Science and Technology, Division of Molecular Science, Gunma University, 1-5-1 Tenjin-cho, Kiryu, Gunma 376-8515.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Inoue
authors.affiliation: the Interdisciplinary Research Organization, University of Miyazaki, Kiyotakecho, Miyazaki 889-1692.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Sakaguchi
authors.affiliation: From the Departments of Cell Biology and.
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: the Department of Biotechnology, Division of Chemistry and Biochemistry, Graduate School of Natural Science and Technology, Okayama University, Okayama 700-8530, and.
authors.forename: Rie
authors.initials: R
authors.lastname: Kinoshita
authors.affiliation: the Department of Biotechnology, Division of Chemistry and Biochemistry, Graduate School of Natural Science and Technology, Okayama University, Okayama 700-8530, and.
authors.forename: Junichiro
authors.initials: J
authors.lastname: Futami
authors.affiliation: the Department of Life Science, Faculty of Science, Okayama University of Science, 1-1 Ridai-cho, Kita-ku, Okayama 700-0005, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Kataoka
authors.affiliation: Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikatacho, Kita-ku, Okayama 700-8558.
authors.forename: Keiji
authors.initials: K
authors.lastname: Iwatsuki
authors.affiliation: From the Departments of Cell Biology and.
authors.forename: Nam-Ho
authors.initials: NH
authors.lastname: Huh
mesh_terms: D040501:Calgranulin A / Q000378:metabolism; D040502:Calgranulin B / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000276:immunology; D011565:Psoriasis / Q000378:metabolism; D034622:RNA Interference; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D040501:Calgranulin A; D040502:Calgranulin B; C120528:HCST protein, human; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic
keywords: Cancer; Cell Biology; Keratinocyte; Psoriasis; Receptor for Advanced Glycation End Products (RAGE)