ABSTRACT

Urokinase-type plasminogen activator (u-PA) is a secreted protease that converts the zymogen plasminogen to plasmin, a trypsin-like serine protease with wide substrate specificity. The u-PA gene has characteristics of both a regulated gene and a housekeeping gene. A homologous cell-free transcription system was developed to investigate hormonal regulation of u-PA gene activation. The most documented negative effect on u-PA gene regulation is that by anti-inflammatory glucocorticoids. Several lines of evidence suggest that a negative regulator is involved in u-PA gene regulation. The stability of u-PA mRNA can be modulated by several means in cultured cells. Protein kinase C seems to regulate u-PA mRNA metabolism as well as u-PA gene expression. Studies of tissue-specific and developmental regulation of u-PA gene expression using, for example, the transgene approach may uncover additional regulatory elements in the u-PA gene and shed light on other modes of gene regulation.