Kringle 1 domain of human tissue-type plasminogen activator is a functional module mediating fibrinogen-stimulated...

The functions of the finger and kringle-2 (K2) domains of human tissue-type plasminogen activator (t-PA) in mediating fibrin-stimulated plasminogenolytic activity are well documented. Contradictory results have been reported for the kringle-1 (K1) domain with respect to this property. To clarify this issue we have deleted the finger and the K2 domains of t-PA according to the exon-intron organization of the gene by site-directed mutagenesis. The resulting derivative (GK1L) was constitutively expressed in permanent clones of Chinese hamster ovary cells. The secreted proteins have been partially purified and characterized by Western blotting. Since the plasminogenolytic activity of GK1L is stimulated by fibrin, the K1 domain of t-PA must be a functional domain in this context.