The cellular and molecular biology of plasminogen activator inhibitor type-2

PAI-2, the most enigmatic member of the serine protease inhibitor gene superfamily, is generally recognised as an inhibitor of urokinase (u-PA) and, to a lesser extent, tissue-type plasminogen activator. The role of plasminogen activator inhibitor type-2 (PAI-2) in the regulation of a u-PA-mediated proteolysis is well established. However, the predominantly cytosolic location of PAI-2 has raised much speculation as to the role this serpin plays in intracellular proteolysis and in particular in the events leading to cellular differentiation and apoptosis. In vitro studies have highlighted the fact that PAI-2 is one of the most tumour necrosis factor (TNF) responsive genes so far described suggesting that PAI-2 may also play a significant role in TNF biology.