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.
|Half-max. binding (µg/ml)
|Influence on cleavage of S-2444
|Influence on plasminogen activation inhibition
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).