STABILIZATION OF PLASMINOGEN-ACTIVATOR INHIBITOR TYPE-1 (PAI-1) ACTIVITY BY ARGININE - POSSIBLE IMPLICATIONS FOR THE INTERACTION OF PAI-1 WITH VITRONECTIN

Plasminogen activator inhibitor type 1 (PAI-1) is an important regulatory protein of the fibrinolytic system. Recently, vitronectin has been identified as a component, encountered both in plasma and in the subendothelial matrix that binds to PAI-1 and stabilises the activity of PAI-1 2- to 3-fold. Mimuro et al1 have shown that dissociation of PAI-1 from the matrix can be achieved with a high concentration of arginine. Here, we demonstrate that purified PAI-1 effectively binds to arginine. Furthermore, we show that binding to arginine increases the half-life of PAI-1 at 37°C by at least 15-fold. This finding greatly facilitates studies on the interaction of PAI-1 with 'target' serine proteases that are hampered by the short half-life (20 min) at 37°C of PAI-1 in the absence of arginine. Other charged amino acids are hardly effective in stabilising PAI-1, whereas non-charged amino acids do not influence the half-life. Arginine residues are clustered in a remarkably hydrophilic carboxyterminal region of vitronectin, the PAI-1 stabilising protein. This region has been implicated in binding to components of the complement and the coagulation system. We postulate that this arginine-rich region of vitronectin is also involved in the binding to and stabilisation of PAI-1. © 1990 Longman Group UK Ltd.