title: TIMP-3 inhibits the procollagen N-proteinase ADAMTS-2.
abstract: ADAMTS-2 is an extracellular metalloproteinase responsible for cleaving the N-propeptides of procollagens I-III; an activity necessary for the formation of collagenous ECM (extracellular matrix). The four TIMPs (tissue inhibitors of metalloproteinases) regulate the activities of matrix metalloproteinases, which are involved in degrading ECM components. Here we delineate the abilities of the TIMPs to affect biosynthetic processing of procollagens. TIMP-1, -2 and -4 show no inhibitory activity towards ADAMTS-2, in addition none of the TIMPs showed inhibitory activity towards bone morphogenetic protein 1, which is responsible for cleaving procollagen C-propeptides. In contrast, TIMP-3 is demonstrated to inhibit ADAMTS-2 in vitro with apparent Ki values of 160 and 602 nM, in the presence of heparin or without respectively; and TIMP-3 is shown to inhibit procollagen processing by cells.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, WI 53706, USA.
authors.forename: Wei-Man
authors.initials: WM
authors.lastname: Wang
authors.forename: Gaoxiang
authors.initials: G
authors.lastname: Ge
authors.forename: N H
authors.initials: NH
authors.lastname: Lim
authors.forename: Hideaki
authors.initials: H
authors.lastname: Nagase
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Greenspan
mesh_terms: D051722:ADAM Proteins / Q000037:antagonists & inhibitors*; D000071096:ADAMTS Proteins; D000071121:ADAMTS4 Protein; D000818:Animals; D055395:Bone Morphogenetic Protein 1; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism; D008666:Metalloendopeptidases / Q000378:metabolism; D051379:Mice; D011348:Procollagen N-Endopeptidase / Q000037:antagonists & inhibitors*; D011485:Protein Binding; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics / Q000378:metabolism; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000235:genetics / Q000378:metabolism*; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics / Q000378:metabolism; D000097792:Tissue Inhibitor of Metalloproteinase-4
chemical_list: D051722:ADAM Proteins; D000071096:ADAMTS Proteins; D000071121:ADAMTS4 Protein; D055395:Bone Morphogenetic Protein 1; D019485:Bone Morphogenetic Proteins; D008666:Metalloendopeptidases; D011348:Procollagen N-Endopeptidase; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D019717:Tissue Inhibitor of Metalloproteinase-3; D019714:Tissue Inhibitor of Metalloproteinases; D000097792:Tissue Inhibitor of Metalloproteinase-4; C088390:TIMP3 protein, human; C000609307:ADAMTS2 protein, human; C000609308:Adamts2 protein, mouse; C525707:Bmp1 protein, mouse