New insights into the molecular mechanisms of the fibrinolytic system

Authors


Dingeman C. Rijken, Erasmus University Medical Center Rotterdam, Department of Hematology, Room Ee1393, Dr Molewaterplein 50. 3015 GE Rotterdam, the Netherlands.
Tel.: +31 10 70 44 723; fax: +31 10 70 44 745.
E-mail: d.rijken@erasmusmc.nl

Abstract

Summary.  Fibrinolysis is regulated by specific molecular interactions between its main components. Activation of plasminogen by tissue-type plasminogen activator (t-PA) is enhanced in the presence of fibrin or at the endothelial cell surface. Urokinase-type plasminogen activator (u-PA) binds to a specific cellular u-PA receptor (u-PAR), resulting in enhanced activation of cell-bound plasminogen. Inhibition of fibrinolysis occurs at the level of plasminogen activation or at the level of plasmin. Assembly of fibrinolytic components at the surface of fibrin results in fibrin degradation. Assembly at the surface of cells provides a mechanism for generation of localized cell-associated proteolytic activity. This review includes novel proteins such a thrombin-activatable fibrinolysis inhibitor (TAFI) and discusses new insights into molecular mechanisms obtained from the rapidly growing knowledge of crystal structures of proteins.

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