title: Large inhibitor of metalloproteinases (LIMP) contains tissue inhibitor of metalloproteinases (TIMP)-2 bound to 72,000-M(r) progelatinase.
abstract: Connective-tissue cells in culture produce a family of metalloproteinases which, once activated, can degrade all the components of the extracellular matrix. These potent enzymes are all inhibited by the tissue inhibitor of metalloproteinases (TIMP), and it was thought that this inhibitor was solely responsible for the inhibition of these enzymes within connective tissue. However, other inhibitors have recently been described, including large inhibitor of metalloproteinases (LIMP) present in the culture medium of human foetal lung fibroblasts. Here we show that a large proportion of the inhibitory activity of LIMP consists of 72,000-M(r)-progelatinase bound to TIMP-2, a recently discovered low-M(r) metalloproteinase inhibitor closely related to TIMP. The physiological implications of the secretion of a complex of 72,000-M(r) progelatinase and TIMP-2 are discussed, and the separation of the complex in 6 M-urea is described.
authors.affiliation: Rheumatology Research Unit, Addenbrooke's Hospital, Cambridge, U.K.
authors.forename: V A
authors.initials: VA
authors.lastname: Curry
authors.forename: I M
authors.initials: IM
authors.lastname: Clark
authors.forename: H
authors.initials: H
authors.lastname: Bigg
authors.forename: T E
authors.initials: TE
authors.lastname: Cawston
mesh_terms: D001345:Autoradiography; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D002850:Chromatography, Gel; D004591:Electrophoresis, Polyacrylamide Gel; D004792:Enzyme Precursors / Q000378:metabolism*; D018093:Gelatinases; D006801:Humans; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism*; D010434:Pepsin A / Q000378:metabolism*; D019716:Tissue Inhibitor of Metalloproteinase-2
chemical_list: D002352:Carrier Proteins; D004792:Enzyme Precursors; D009363:Neoplasm Proteins; D019716:Tissue Inhibitor of Metalloproteinase-2; D010434:Pepsin A; D018093:Gelatinases; D008666:Metalloendopeptidases; C069860:progelatinase