The role of the finger and growth factor domains in the clearance of tissue-type plasminogen activator by hepatocytes

Abstract

The relative contribution of the finger/growth factor domains of tissue- type plasminogen activator (t-PA) and of the other t-PA domains to the clearance of t-PA by hepatocytes was investigated, A recombinant finger/growth factor construct inhibited t-PA and t-PA/plasminogen activator inhibitor type-1 degradation with an IC50 of 1800 nM, whereas a t-PA mutant lacking the finger and growth factor domains inhibited degradation 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 domains of the t-PA molecule.