THE PLASMA CARBOXYPEPTIDASES AND THE REGULATION OF THE PLASMINOGEN SYSTEM

Central to the regulation of the plasminogen system, a proteolytic net work that mediates degradation of fibrin and facilitates cell migratio n, is the binding of plasminogen to carboxy-terminal lysines. These re sidues occur either naturally on pZasnzin substrates or cell surfaces or are generated as a consequence of partial plasmin degradation. The basic carboxypeptidases of plasma are capable of removing such carboxy -terminal lysines. Carboxypeptinase N, which is constitutively active, suppresses plasminogen binding to cell surfaces, plasma carboxypeptid ase B, which must be proteolytically activated, not only suppresses ce llular binding of plasminogen bur also dampens fibrinolysis. Thus, the plasma carboxypeptidases may constitute an important regulatory pathw ay for controlling the activity of the plasminogen system in physiolog ic, pathophysiologic, and pharmacologic circumstances. (C) 1997, Elsev ier Science Inc.