Thrombin-activatable fibrinolysis inhibitor (TAFI, plasma procarboxypeptidase B, procarboxypeptidase R, procarboxypeptidase U).
Recently, a new inhibitor of fibrinolysis was described, which downregulated fibrinolysis after it was activated by thrombin, and was therefore named TAFI (thrombin-activatable fibrinolysis inhibitor; EC 3.4.17.20). TAFI turned out to be identical to the previously described proteins, procarboxypeptidase U, procarboxypeptidase R, and plasma procarboxypeptidase B. Activated TAFI (TAFIa) downregulates fibrinolysis by the removal of carboxy-terminal lysines from fibrin. These carboxy-terminal lysines are exposed upon limited proteolysis of fibrin by plasmin and act as ligands for the lysine-binding sites of plasminogen and tissue-type plasminogen activator (t-PA). Elimination of these lysines by TAFIa abrogates the fibrin cofactor function of t-PA-mediated plasminogen activation, resulting in a decreased rate of plasmin generation and thus downregulation of fibrinolysis. In this review, the characteristics of TAFI are summarized, with an emphasis on the pathways leading to activation of TAFI and the role of TAFIa in the inhibition of fibrinolysis. However, it cannot be ruled out that TAFI has other, as yet undefined, functions in biology.
Bouma
B N
BN
Thrombosis and Haemostasis Laboratory, Department of Haematology, University Medical Center, Utrecht, The Netherlands. bouma@scripps.edu
Meijers
J C M
JC
D000818:Animals; D025901:Carboxypeptidase B2 / Q000737:chemistry* / Q000502:physiology*; D015536:Down-Regulation; D005341:Fibrinolysin / Q000737:chemistry; D005342:Fibrinolysis; D006801:Humans; D008239:Lysine / Q000737:chemistry; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D018180:Thrombomodulin / Q000737:chemistry; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000737:chemistry
D018180:Thrombomodulin; D025901:Carboxypeptidase B2; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin; D008239:Lysine