Search Organism: All OrganismsArabidopsis thalianaBacillus subtilis 168Bos taurusCaenorhabditis elegansCanis familiarisDanio rerioDrosophila melanogasterEquus caballusEscherichia coli K12Gallus gallusHomo sapiensMacaca mulattaMus musculusNematostella vectensisOryza sativaPan troglodytesRattus norvegicusSaccharomyces cerevisiaeSchizosaccharomyces pombeStrongylocentrotus purpuratusTakifugu rubripesXenopus laevis home support contribute downloads mirrors about us J. Biol. Chem. Jun (1994); 269(25):17199-205 Regulation of protease nexin-1 target protease specificity by collagen type IV. Donovan FM, Vaughan PJ, Cunningham DD Department of Microbiology and Molecular Genetics, University of California, Irvine 92717. Abstract: Recent studies have shown that serine protease inhibitors can be regulated in their activity, specificity, and location by glycoprotein or extracellular matrix (ECM) co-factors. Protease nexin-1 (PN-1) is a member of the serpin superfamily of serine protease inhibitors which can rapidly inhibit thrombin, urokinase, and plasmin. PN-1 binds tightly to and is regulated by the ECM. This interaction accelerates the inhibition of thrombin by PN-1 and blocks urokinase and plasmin inhibition by PN-1. Previous work showed that heparan sulfate proteoglycan is largely responsible for the acceleration of thrombin inhibition by PN-1. Our current studies were directed at identifying ECM component(s) that decreased the ability of PN-1 to inhibit urokinase and plasmin. These studies showed that collagen type IV decreased the formation of SDS-stable complexes between urokinase or plasmin and PN-1 without affecting formation of complexes between thrombin and PN-1. The second order rate constant for inhibition of urokinase by PN-1 was markedly decreased with increasing collagen type IV, whereas the second order rate constant for inhibition of thrombin by PN-1 was unaffected by addition of collagen type IV. Other ECM components (collagen type I, vitronectin, fibronectin, and heat-denatured collagen type IV) did not affect complex formation or the rate of inhibition of proteases by PN-1, indicating that these effects were specific to collagen type IV. Binding of PN-1 to immobilized collagen type IV was demonstrated using an enzyme-linked immunosorbent assay; the concentration of PN-1 necessary to obtain 50% saturation of the immobilized collagen type IV binding sites was approximately 15 nM. Collagen type IV was also copurified with PN-1 from fibroblast-conditioned medium. These results demonstrate a novel regulation of serpin specificity in which an ECM co-factor decreased the inhibition of certain proteases by the serpin without affecting the inhibition of its target protease. [PUBMED: 8006028] Copyright © 2007, Tyers Lab, The Samuel Lunenfeld Research Institute, Mount Sinai Hospital, All Rights Reserved. terms and conditions - privacy policy - Osprey Network Visualization System BioGRID: A General Repository for Interaction Datasets. Chris Stark, Bobby-Joe Breitkreutz, Teresa Reguly, Lorrie Boucher, Ashton Breitkreutz, Mike Tyers. Nucleic Acids Res. Jan 1;34:D535-9.