TAFI (thrombin-activatable fibrinolysis inhibitor) is a recently discovered plasma protein that can be activated by thrombin-catalyzed proteolysis to a carboxypeptidase B-like enzyme that inhibits fibrinolysis. This work shows that the thrombin-thrombomodulin complex, rather than free thrombin, is the most likely physiologic activator. Thrombomodulin increases the catalytic efficiency of the re...

The role of heparin in promoting the reaction between the plasma inhibitor, antithrombin I l l , and several proteolytic enzymes involved in blood coagulation is not clearly understood. Rosenberg and his colleagues (see, for example, Rosenberg & Damus, 1973; Highsmith & Rosenberg, 1974) have claimed that heparin binding modifies the shape of the anti-thrombin I I I molecule, thus exposing a vul...

Whereas crude bovine thrombin activated single-chain urokinase-type plasminogen activator (scu-PA), otherwise called pro-urokinase (pro-UK). purified human thrombin converted pro-UK (scu-PA) to a two-chain form that had no amidolytic activity. The two chains (M 33.000 and 22.000) were disulfide linked and resistant to subsequent activation by plasmin. By contrast. thrombin did not mactivate tis...

Whereas crude bovine thrombin activated single-chain urokinase-type plasminogen activator (scu-PA), otherwise called pro-urokinase (pro-UK). purified human thrombin converted pro-UK (scu-PA) to a two-chain form that had no amidolytic activity. The two chains (M 33.000 and 22.000) were disulfide linked and resistant to subsequent activation by plasmin. By contrast. thrombin did not mactivate tis...

In a proteasome-lacking mutant of Streptomyces coelicolor A3(2), an intracellular enzyme with chymotrypsinlike activity, absent from the wild type, was detected. Complementation that restored proteasome function did not suppress expression of the endopeptidase. Since the enzyme was not found in two other S. coelicolor proteasome mutants, its expression probably resulted from a secondary mutatio...

BACKGROUND Tubulointerstitial fibrosis contributes to the progression of many forms of glomerular disease and to end-stage renal failure. Inflammatory mediators generated during glomerular injury may induce tubulointerstitial lesions by stimulating tubular cells. Thrombin has multiple biological functions in addition to its role in haemostasis and has been detected in the urine of patients with...

Proliferation of smooth muscle cells (SMCs) in atherosclerosis may be modulated by several growth regulatory molecules. At least two mitogens for SMCs, platelet-derived growth factor (PDGF) A-chain and heparin-binding epidermal growth factor-like growth factor (HB-EGF), can be produced by SMCs themselves and may stimulate smooth muscle proliferation in an autocrine or paracrine fashion. We exam...

The initiation phase of enzyme generation in a reconstituted model of the tissue factor (TF) pathway to thrombin was evaluated. At 1.25 pM added TF, no thrombin generation was observed in the absence of factor V. The substitution of factor Va for factor V increased the rate of thrombin generation. Factor X activation during the initiation phase was not influenced by the absence of factor VIII o...