[Molecular biology of tissue-type plasminogen activator (t-PA) and clinical application of recombinant t-PA].
Activation of blood fibrinolysis is initiated by the activation of plasminogen to plasmin by plasminogen activator (PA). The plasmin thus produced can degrade fibrin, the main component of thrombus. Tissue-type PA (t-PA) which is mainly secreted from vascular endothelial cells possesses a high affinity for fibrin in contrast to urokinase-type PA (u-PA). Enzymatic activity of t-PA is expressed in either single-chain form or two-chain form. Further, t-PA activity enhanced markedly in the presence of fibrin; 600-1,000-fold increase. Thus, the thrombolytic therapy is now being performed by using t-PA. The mechanism for thrombolysis by t-PA involves the activation of fibrinolytic system on the fibrin surface. The kringle 2 domain of t-PA molecule plays an important role on the binding to fibrin. But in single-chain t-PA, finger domain plays a role for its binding to fibrin. Recent studies have revealed that the t-PA specific receptor (t-PAR) is expressed on the endothelial cells which localizes t-PA activity by fixing t-PA around the cells.
Fukao
H
H
Department of Physiology, Kinki University School of Medicine.
Matsuo
O
O
D000595:Amino Acid Sequence; D006801:Humans; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000627:therapeutic use; D010959:Tissue Plasminogen Activator / Q000737:chemistry* / Q000502:physiology* / Q000627:therapeutic use
D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator