uPA (urokinase-type plasminogen activator) and tPA (tissue plasminogen activator), which are serine proteases and members of the trypsin family, are essential to the intrinsic coagulation system. tPA is primarily involved in fibrinolysis, whereas uPA principally mediates cell migration and tissue remodeling processes. uPA and tPA are responsible for cleaving plasminogen, a large serum β-globulin that is deposited on the Fibrin strands within a thrombus. uPA and tPA preferentially target plasminogen at the Arg-Val bond to produce plasmin (also designated fibrinolysin), which is a trypsin-like enzyme that acts on Arg-Lys bonds in Fibrin and Fibrinogen and contributes to the systematic activation of the coagulation cascade. uPA and tPA each consist of two chains that are designated A and B. The A chain of uPA can be cleaved, resulting in low and high molecular mass forms. uPA and tPA are regulated by the serpin family members PAI-1 and PAI-2, which are serine proteinase inhibitors that complex with uPA, tPA and other targeted proteinases and then slowly disassociate to produce cleaved species that fold into stable inactive conformations.
