Signal Transduction Chains Involved in the Control of the Fibrinolytic Enzyme Cascade

  • Wolf-Dieter Schleuning
  • Robert L. Medcalf
Part of the NATO ASI Series book series (NSSA, volume 191)


The fibrinolytic enzyme cascade is a summary term for several regulatory serine proteases and serine protease inhibitors, which cooperate in the digestion of extracellular matrix protein in processes of tissue repair, growth, and remodelling. Tissue-type plasminogen activator (t-PA) and urinary-type plasminogen activator (u-PA) activate the proenzyme plasminogen by the cleavage of a single peptide bond, converting it into plasmin, a proteolytic enzyme with a specificity similar to the pancreatic digestive enzyme trypsin. Plasminogen is synthesized in the liver and secreted into the bloodstream where it circulates in relatively large amounts (80160 mg/l). Blood plasma plasminogen provides a reservoir of proteolytic activity which is recruited for the removal of fibrin deposits or for the digestion of extracellular matrix proteins during morphogenesis, wound healing or malignant growth. t-PA and u-PA are structurally and enzymatically related. Both proteins display a characteristic mosaic molecular architecture: they consist of a series of structural motifs homologous to other proteins. Thus, starting from the amino terminus, t-PA is composed of a “finger” domain, which is found tandemly arranged in fibronectin; an epidermal growth factor (EGF) like motif, found likewise in various blood clotting factors, receptor proteins and developmentally regulatory proteins; two “kringle” regions, present in u-PA, plasminogen, prothrombin, clotting factor XII and apolipoprotein (a) and finally a sequence homologous to the pancreatic proteases trypsin, chymotrypsin, elastase and kallikrein. The “finger”- and one of the two “kringle”-domains are absent in u-PA.


Plasminogen Activator Plasminogen Activator Inhibitor Plasminogen Activator Activity Cell BioI Signal Transduction Chain 


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Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • Wolf-Dieter Schleuning
    • 1
  • Robert L. Medcalf
    • 1
  1. 1.Central Hematology LaboratoryUniversity of Lausanne Medical School (CHUV)CH-LausanneSwitzerland

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