Modulation and mapping of a human plasminogen activator by cell fusion

Neoplastic cells, transformed cells and some normal mammalian cells secrete large amounts of plasminogen activator (PA), an arginine-specific protease which converts plasminogen to plasmin. To study the regulation of PA, we have obtained two classes of mouse-human somatic cell hybrids. PG19, a mouse PA+ cell line, was fused with C32 (human PA+) or human diploid fibroblasts (PA-). All hybrids secreted PA. Human- and mouse-specific forms of PA were distinguished in these hybrids by electrophoretic methods. While all hybrids produced the murine PA, many produced the human PA and some did not. All hybrids which produced human PA had chromosome 6 in common. The absence of each of the other human chromosomes did not affect PA expression, while the absence of chromosome 6 correlated with the lack of human PA. We conclude that chromosome 6 carries the structural gene for human PA. These experiments also show that the fusion of mouse PA+ cells with human PA- cells results in the activation of the human PA gene.