Regulation and interactions in the activation of cell-associated plasminogen

The main components in plasminogen activation include plasminogen, tissue plasminogen activator (tPA), urokinase plasminogen activator (uPA), urokinase plasminogen activator receptor ( uPAR), and plasminogen activator inhibitors-1 and - 2 (PAI-1, PAI-2). These components are subject to extensive regulation and interactions with for example, pericellular adhesion molecules. Although uPA and tPA are quite similar in structure and have common inhibitors and physiological substrates, their physiological roles are distinct. Traditionally, the role of tPA has been in fibrinolysis and that of uPA in cell migration, especially in cancer cells. Recently several targets for tPA/plasmin have been found in neuronal tissues. The functional role of the PAIs is no longer simply to inhibit overexpressed plasminogen activators, and PAI-2 has an unidentified role in the regulation of cell death.