Glial-derived neurite-promoting factor is a slow-binding inhibitor of trypsin, thrombin, and urokinase.
Glial-derived neurite-promoting factor was found to be a slow-binding inhibitor of trypsin, urokinase, and thrombin. The kinetic mechanism of the inhibition differs among the three proteases. With trypsin and urokinase, an initial protease-factor complex formed which isomerized to a tighter complex. For thrombin, however, no initial complex was kinetically observed. The dissociation constants of the equilibrium complexes of the factor with trypsin, urokinase, and thrombin were 17, 280, and 18 pM, respectively, and the apparent second-order rate constants for the interaction of the factor with these enzymes were, respectively, 4.7 X 10(6), 1.2 X 10(5), and 2.1 X 10(6) M-1S-1. Heparin increased the rate at which the factor reacted with thrombin by over 40-fold to 8.9 X 10(7) M-1S-1 and decreased the dissociation constant of the complex by over 80-fold to 0.3 pM. The values obtained for the apparent second-order rate constants when compared with the kinetics of neurite induction by the factor indicate that the neurite-promoting activity of the factor is not due to the inhibition of urokinase but could be due to the inhibition of an enzyme with a specificity similar to that of thrombin or trypsin. Comparison of the values of the apparent second-order rate constants obtained for the factor with those obtained for protease nexin suggests that these two molecules are very similar in their inhibitory properties.
D016564:Amyloid beta-Protein Precursor; D002352:Carrier Proteins / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D011480:Protease Inhibitors / Q000494:pharmacology; D058255:Protease Nexins; D011956:Receptors, Cell Surface; D013917:Thrombin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014361:Trypsin Inhibitors / Q000378:metabolism*; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors* / Q000378:metabolism
D016564:Amyloid beta-Protein Precursor; D002352:Carrier Proteins; D011480:Protease Inhibitors; D058255:Protease Nexins; D011956:Receptors, Cell Surface; D014361:Trypsin Inhibitors; D006493:Heparin; D013917:Thrombin; D014568:Urokinase-Type Plasminogen Activator