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The keratinocyte differentiation process is under the control of signals that balance proliferation and cell differentiation. Del-1, a member of the annexin superfamily, is expressed in the epidermis and it is one of the most strongly induced genes in keratinocytes at the onset of differentiation. In this study, we show that Del-1-null mice develop epidermal defects that include a thinner and compromised epidermis and reduced differentiation. Del-1-null keratinocytes fail to down-regulate EGFR and phosphorylated Akt. This defect is corrected in vitro when Del-1 is expressed with the epidermal growth factor receptor (EGFR). Del-1 regulates epithelial growth via anti-mitogenic/differentiation-enhancing effects. Epidermal growth factor treatment increased the autocrine function of Del-1, as Del-1 neutralizing antibodies reduced epithelial growth in Del-1-null keratinocytes. Proliferating epidermal growth factor receptor (EGFR) expressing cells (the suprabasal layers) express high levels of Del-1. Altogether, this study demonstrates that Del-1 is induced in the suprabasal layers of the epidermis and that it functions as a negative regulator of cell growth. Del-1 binds to membrane phospholipids, which results in PI-4-phosphate accumulation. This activates several signaling pathways that counterbalance EGFR signaling.In the quest for ever-more sophisticated power tools, from sanders to power drills to circular saws, woodworkers have long turned their attention to the electric impact driver, the versatile, cordless screw driver that nails, screws and drills fasteners with just an impact. Meanwhile the huge selection of Woodworker's Supply tools in the store can keep you busy for hours as you find out how to use what you bought.
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