THE INTERACTION OF STREPTOKINASE WITH PLASMINOGEN. I. FUNCTIONAL PROPERTIES OF THE ACTIVATED ENZYME.

In past years numerous studies have been concerned with the role of the bacterial protein, streptokinase, in the activation of the proenzyme plasminogen to plasmin, as well as with the hydrolytic properties of plasmin itself. One of the questions raised was whether the protease and esterase activities of plasmin are due to the same enzyme or to two different ones. If the second alternative was true, did the two enzymes develop from a common precursor, or from two different plasminogens. Other studies were aimed at the clarification of the nature of “activator activity,” i.e. the ability of small amounts of streptokinasehuman plasminogen mixtures to activate bovine plasminogen (the latter can be activated neither by streptokinase alone nor by human plasmin). The substance responsible for this catalytic conversion (activator) was concluded to be a complex between streptokinase and a protein present in solutions of human plasminogen. The identity of this cofactor, termed “proactivator,” has been a much debated question. Human plasminogen, plasmin, or a contaminating protein were at various times considered as possibilities. It was generally assumed that the activation of human plasminogen itself was mediated by the same streptokinase-proactivator complex which was responsible for the activation of bovine plasminogen. Kline and Fishman (1) in a recent publication have provided convincing evidence for the identification of human plasmin as the proactivator for the activation of bovine plasminogen. Our own results have independently led us to similar conclusions (2,3). The object of the work reported in this and the following paper was to answer the questions raised above. The experimental approach was to study the effects of different concentrations of streptokinase on the development of activities toward different substrates and to correlate their rates of development. The complex over-all picture which has emerged from these studies is summarized in Table I. The present paper deals with the stable enzymatic properties of plamin and streptokinase-plasmin as they occur in solutions containing variable proportions of the two components. The kinetics of activator formation and of activation are the subject of the next paper in this series.