Identification of Modified Streptokinase as the Activator of Bovine and Human Plasminogen

This paper reports observations made of the events which occur when two apparently enzymatically inactive proteins, streptokinase and plasminogen, interact in the correct ratio to form a complex which is an activator of plasminogen. The unique physical and functional properties of this plasminogen activator complex were demonstrated by: (a) observation of the complex in polyacrylamide gel systems and (b) by its capacity to convert bovine or guinea pig plasminogen to plasmin. When the complex was dissociated on a sodium dodecyl sulfate polyacrylamide gel system, two components having physical properties similar to those of the original inactive components were recovered. However, following dissociation, the component which was similar to plasminogen had plasmin activity, and the component which was similar to streptokinase had bovine plasminogen activator activity. The completeness of the separation of the two components was examined revealing that approximately 1 mole of streptokinase contaminated every 1600 moles of the dissociated plasmin component and 1 mole of plasmin contaminated every 1000 moles of the dissociated streptokinase component. The activator activity of the dissociated streptokinase component decreased less than 10% upon a reduction of the plasmin contaminant by 97%. It was therefore concluded that the dissociated streptokinase component bore the site for bovine plasminogen activator activity. Studies of the dissociated streptokinase component indicated that there was no demonstrable change in molecular weight. From these data and the demonstration that the dissociated streptokinase activated human plasminogen as well as bovine plasminogen, a model describing the mechanism of streptokinase activation of human plasminogen was constructed. In this model streptokinase interacts with the plasmin contaminating human plasminogen to form a modified streptokinase which in turn acts on human plasminogen in a positive feedback.