Description of Plasminogen

Plasminogen (Pg) is synthesized in the liver and circulates in plasma at a concentration of ~200 μg/ml (~2.3 μM). Plasminogen is a single-chain glycoprotein of ~88 kDa that consists of a catalytic domain followed by five kringle structures. Within these kringle structures are four low-affinity lysine binding sites and one high-affinity lysine binding site. It is through these lysine binding sites that plasminogen binds to fibrin and to α2antiplasmin. Native plasminogen (glu-plasminogen) exists in two variants that differ in their extent of glycosylation, and each variant has up to six isoelectric forms with respect to sialic acid content, for a total of 12 molecular forms. Activation of glu-plasminogen by the plasminogen activators urokinase (UPA), or tissue plasminogen activator (tPA) occurs by cleavage after residue Arg560 to produce the two-chain active serine protease plasmin. In a positive feedback reaction, the plasmin generated cleaves an ~8 kDa peptide from glu-plasminogen, producing lys77-plasminogen which has a higher affinity for fibrin and when bound is a preferred substrate for plasminogen activators such as urokinase. Additional activators of plasminogen include kallikrein and activated factor XII. The primary inhibitor of plasmin in plasma is α2antiplasmin. Other physiological inhibitors of plasmin include α2macroglobulin and antithrombin^1-3.

References and Reviews

1. Bachmann F; The Plasminogen-Plasmin Enzyme System; in Hemostasis and Thrombosis, 3^rd Edition, eds. RW Colman, J Hirsh, VJ Marder and EW Salzman, pp. 1592-1622, J.B. Lippincott Co., Philadelphia PA, USA, 1994.
2. Castellino FJ, Powell JR; Human Plasminogen; Methods in Enzymology 80, pp 365-378, 1981.
3. Wiman B, Collen D; Molecular Mechanism of Physiological Fibrinolysis; Nature 272, pp 548-553, 1978.