Urokinase-type plasminogen activator and tissue-type plasminogen activator (uPA and tPA)

Urokinase-type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA) are two closely related multidomain serine proteases that catalyze the conversion of plasminogen to plasmin, a critical enzyme in the dissolution of fibrin blood clots (fibrinolysis)[1][3][7]. Both enzymes share similar structural motifs, but serve distinct physiological functions: tPA mainly acts within the vascular system to maintain hemostasis and dissolve fibrin polymers, while uPA predominantly regulates pericellular fibrinolysis, extracellular matrix degradation, and tissue remodeling, especially in contexts such as cancer invasion and metastasis[1][2][3][4][5][7]. uPA is secreted as a proenzyme (pro-uPA) and becomes active when bound to the urokinase receptor (uPAR), whereas tPA activity is enhanced by interaction with fibrin and is also present in the nervous system, where it contributes to processes such as synaptic plasticity[1][4]. Both targets are clinically relevant for thrombolytic therapy (e.g., treatment of acute myocardial infarction and stroke), are implicated in cancer progression and tissue remodeling, and are being investigated as biomarkers and therapeutic targets.

Other names

urokinaseurokinase-type plasminogen activator (uPA)tissue-type plasminogen activator (tPA)plasminogen activatorsserine proteases

Induction of fibrinolysis by converting plasminogen to plasmin, Thrombolysis, Extracellular matrix remodeling via plasmin activation