Urokinase-urokinase receptor interaction: non-mitogenic signal transduction in human epidermal cells

We studied non-mitogenic signal transduction in a human cell line of epidermal origin which is induced to chemotaxis following stimulation with human urokinase-type plasminogen activator (u-PA) or with the amino-terminal fragment (ATF) of u-PA A chain, which specifically interacts with the cellular receptor. U-PA and ATF stimulated the formation of diacylglycerol (DAG) independently of inositol lipid and phosphatidylcholine turnover, but concomitantly with de novo synthesis from glucose, thus resembling the DAG neosynthesis activated by insulin. DAG was measured in normal epidermal cells and in cells transfected with the human u-PA receptor (u-PAR) gene and stimulated with u-PA or ATF. Transfected clones showed an increase of cell motility under an ATF gradient in vitro as well as an increase of DAG production. These findings identify a novel mechanism of second messenger formation that conveys chemotactic signals upon stimulation of the u-PAR.