Plasminogen activator and the membrane of transformed cells

Studies have been conducted on the enzyme plasminogen activator (PA) in cultures of RSV transformed CEF. The enzyme exists in two forms, a soluble extracellular form (PAex) and a cell-associated form that is firmly bound to specific membranes (PAmem) when cell homogenates are subfractionated. Both forms of the enzyme are induced in a synergistic fashion by treatment of RSVCEF with the tumor promoter phorbol myristate acetate (PMA). The induction of the enzyme by PMA has allowed for the purification of PAex. In addition, PMA treatment of RSVCEF causes pronounced morphological alterations in culture. The use of protease inhibitors, [3H]-DFP, and a direct fluorometric assay for PA indicate that the morphological changes are due to the direct catalytic action of PA, independent of plasminogen, until now its only known natural substrate. Recent experiments suggest that PAmem is responsible for the morphological changes and that residual amounts of LETS protein are lost from the cell surface and substratum coincident with the morphological changes. The possible role of serine proteases in regulatory cellular behavior in transformed or tumor promoter-treated cells is discussed.