Urokinase-type Plasminogen Activator (u-PA)

u-PA is a 55kD two chain plasminogen activator produced by plasmin or kallikrein cleavage of single-chain precursor molecule scu-PA at the site of the Lys-158 - Ileu159 peptide bond. A single disulphide bond links the two chains of the u-PA molecule: the B-chain contains the catalytic site and the A-chain contains a kringle-domain and a growth factor domain. Thrombin is capable of cleaving scu-PA at position Arg-156 - Phe-157 resulting in an inactive 2-chain u-PA.

Single chain u-PA has some intrinsic activities which represents less than 5% of the activity of 2-chain u-PA. However, scu-PA is capable of activating plasminogen to plasmin, a process which is stimulated in the presence of fibrin and which, especially in vivo, mediates fibrin specific thombolytic activity.

As compared to tissue-type plasminogen activator which binds to forming fibrin, u-PA binds to specific receptors on several cell types, thereby focusing its plasminogen activating and proteolytic activity on the cell surface.

u-PA circulates in its single chain form in plasma in an average concentration of 1 to 2 ng/ml. Its concentrations is increased in cases of some malignancies, especially those of the urogenital and gastrointestinal tracts.

Purified human urinary high molecular weight urokinase according to the method of Huber et al. (k. Huber, J. Kircheimer, B.R. Binder: Characterization of specific anti-human urokinase antibody: development of a sensitive competitive radioummunoassay for urokinase antigen. J. Lab. Clin. Med. 103: 684-694, 1984).