RRC ID 45165
著者 Sakaguchi M, Murata H, Aoyama Y, Hibino T, Putranto EW, Ruma IM, Inoue Y, Sakaguchi Y, Yamamoto K, Kinoshita R, Futami J, Kataoka K, Iwatsuki K, Huh NH.
タイトル 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.
ジャーナル J Biol Chem
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.
巻・号 289(34)
ページ 23389-402
公開日 2014-8-22
DOI 10.1074/jbc.M114.573071
PII S0021-9258(20)32020-2
PMID 25002577
PMC PMC4156043
MeSH Calgranulin A / metabolism Calgranulin B / metabolism Cells, Cultured Humans Keratinocytes / metabolism* Killer Cells, Natural / immunology Psoriasis / metabolism RNA Interference Receptor for Advanced Glycation End Products Receptors, Immunologic / metabolism* Signal Transduction*
IF 4.238
引用数 18
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ヒト・動物細胞