THE ROLE OF THE FINGER AND GROWTH-FACTOR DOMAINS IN THE CLEARANCE OF TISSUE-TYPE PLASMINOGEN-ACTIVATOR BY HEPATOCYTES

The relative contribution of the finger/growth factor domains of tissu e-type plasminogen activator (t-PA) and of the other t-PA domains to t he clearance of t-PA by hepatocytes was investigated. A recombinant fi nger/growth factor construct inhibited t-PA and t-PA/plasminogen activ ator inhibitor type-1 degradation with an IC50 of 1800 nM, whereas a t -PA mutant lacking the finger and growth factor domains inhibited degr adation with an estimated IC50 of 1200 nM. In comparison the IC50 of t -PA was found to be approximately 10 nM. Clearance of t-PA by human or rat hepatoma cells was not inhibited by high concentrations of fucose (50 mM), which suggests that the fucose on Thr-61 is not involved in clearance by these cells. These results suggest that the binding of t- PA involves several low affinity binding sites located on distinct dom ains of the t-PA molecule.