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.

The receptor for advanced glycation end products is involved in the pathogenesis of many inflammatory, degenerative, and hyperproliferative diseases, including cancer. Previously, we revealed mechanisms of downstream signaling from ligand-activated which recruits TIRAP/MyD88. Here, we showed that DNAX-activating protein 10 (DAP10), a transmembrane adaptor protein, also binds to By artificial oligomerization of alone or we found that heterodimer formation resulted in a marked enhancement of Akt activation, whereas homomultimeric interaction of duanyu1648 led to activation of caspase 8. Normal human epidermal keratinocytes exposed to S100A8/A9, a ligand for duanyu1648, at a nanomolar concentration mimicked the pro-survival response of duanyu1648-DAP10 interaction, although at a micromolar concentration, the cells mimicked the pro-apoptotic response of 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 duanyu1648-DAP10 interaction. Functional blocking of DAP10 in the cell lines abrogated the Akt phosphorylation from S100A8/A9-activated duanyu1648, eventually leading to an increase in apoptosis. Finally, S100A8/A9, duanyu1648, and DAP10 were overexpressed in the psoriatic epidermis. Our findings indicate that the functional interaction between duanyu1648 and DAP10 coordinately regulates S100A8/A9-mediated survival and/or apoptotic response of keratinocytes. © 2014 by The American Society for Biochemistry and Inc.

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