Biochemical and biological aspects of the plasminogen activation system.
Plasminogen activators (PAs) are specific proteolytic enzymes which convert the inactive proenzyme plasminogen to plasmin. The plasmin formed is a potent and nonspecific protease which cleaves blood fibrin clots and several other extracellular proteins. In addition to their primary role in the initiation of fibrinolysis, PAs are implicated in a variety of basic biological processes, such as, degradation of the extracellular matrix, tumor invasiveness, tissue remodelling, and cellular differentiation. This review describes recent observations on the biochemical and biophysical characteristics of the different components of the plasminogen activation system. This complex system includes: the proenzymes of tissue type PA (tPA) and urokinase type PA (uPA); the active enzymes tPA, uPA and plasmin; the substrate plasminogen; several natural inhibitors of PA and plasmin activity; and the cellular receptors that bind the proenzymes, enzymes, and inhibitor-enzyme complexes. Through the coordinated interactions of these components, the location, timing, and extent of potent proteolytic activity is controlled. Recent findings on the structure, properties, biological functions, and regulation of the different components of the plasminogen activation cascade are reviewed. Current methods for assay of the amount and activity of the enzymes, inhibitors, and receptors are described. Observations implying specific functions of the system in health and disease, and its potential utilization for diagnosis are examined. Specifically, the potential application of PAs as laboratory markers of neoplasia, as diagnostic tools in diseases of the blood clotting system, their use for monitoring of thrombolytic therapy, and their possible relevance in certain disease states are described.
Department of Clinical Biochemistry, Hadassah Medical Center, Jerusalem, Israel.
M
M
Mayer
D001172:Arthritis, Rheumatoid / Q000097:blood; D014408:Biomarkers, Tumor / Q000032:analysis; D003920:Diabetes Mellitus / Q000097:blood; D005342:Fibrinolysis; D006801:Humans; D008991:Monitoring, Physiologic; D010960:Plasminogen Activators / Q000032:analysis / Q000502:physiology*
D014408:Biomarkers, Tumor; D010960:Plasminogen Activators