Urokinase type plasminogen activator serine proteases

Urokinase-type plasminogen activator (uPA, urokinase) is synthesized by endothelial and tumor cells as a single-chain glycoprotein (scuPA) without catalytic activity. When it is converted to a two-chain protein (tcuPA) by plasmin, an active serine protease center develops, which activates plasminogen. Thus, uPA (55 kDa) results in the amplification of fibrinolysis. 

Takayama TK, McMullen BA, Nelson PS, Matsumura M, Fujikawa K. Characterization of hK4 (Prostase), a prostate-specific serine protease Activation of the precursor of prostate specific antigen (pro-PSA) and single-chain urokinase-type plasminogen activator and degradation of prostatic acid phosphatase. Biochemistry 2001 40 15341-15348. 

The fibrinolytic system is activated in response to the presence of an intracellular thrombus or clot. The process of clot dissolution is initiated by the conversion of plasminogen to plasmin. Plasminogen activation is catalyzed by two endogenous highly specific serine proteases, urokinase-type plasminogen activator and tissue-type plasminogen activator (t-PA) (see Chapter 31). 

Urokinase-type plasminogen activator (uPA ) [82] is a trypsin-like serine protease [83] that, when bound to the extracellular membrane-associated urokinase-... 

Breitenbucher, J.G., Hui, H.C, Vemer, E., Luong, C., Liu, L., and Sprengeler, P.A. (2001) Exploiting subsite SI of trypsin-like serine proteases for selectivity potent and selective inhibitors of urokinase-type plasminogen activator. Journal of Medicinal Chemistry, 44, 3856-3871. 

Additional serine proteases have been found in chronic wounds and neutrophils probably are also the primary source of these enzymes. These include cathepsin G, another cationic serine protease with broad substrate specificity, urokinase-type plasminogen activator (itfA), and protease 3 (3,32-35). In all probability, when looked for, elevated levels of additional neutrophil proteases will be found in chronic dermal ulcers. 

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