Thrombin, thrombomodulin and TAFI in the molecular link between coagulation and fibrinolysis.
The thrombin thrombomodulin dependent activation of the plasma protein TAFI (Thrombin Activatable Fibrinolysis Inhibitor) and Subsequent Inhibition of Fibrinolysis by the TAFIa is described. Work to date indicates that TAFIa is a carboxypeptidase B enzyme that suppress fibrinolysis most likely by down regulating the cofactor functions of partially degraded fibrin. The existence of TAFI provides the explanation for the apparent profibrinolytic effect of activated protein C. and implies the existence of an explicit molecular connection between the blood coagulation of fibrinolytic cascades that is expressed through the thrombin thrombomodulin dependent activation of TAFI. Thus, thrombin generation can, in principle, result in the suppression of fibrinolysis.
Nesheim
M
M
Department of Biochemistry, Queen's University, Kingston, Ontario, Canada. nesheimm@post.queensu.ca
Wang
W
W
Boffa
M
M
Nagashima
M
M
Morser
J
J
Bajzar
L
L
D000595:Amino Acid Sequence; D001777:Blood Coagulation / Q000502:physiology*; D025901:Carboxypeptidase B2; D002268:Carboxypeptidases / Q000302:isolation & purification / Q000502:physiology*; D004789:Enzyme Activation; D005342:Fibrinolysis / Q000502:physiology*; D006801:Humans; D013917:Thrombin / Q000502:physiology*; D018180:Thrombomodulin / Q000502:physiology*
D018180:Thrombomodulin; D002268:Carboxypeptidases; D025901:Carboxypeptidase B2; D013917:Thrombin