title: Cellular activation of proMMP-13 by MT1-MMP depends on the C-terminal domain of MMP-13.
abstract: Procollagenase-3 (proMMP-13) can be activated by soluble or cell associated membrane type matrix metalloproteinase 1 (MT1-MMP). In this study we show that the cell based activation of proMMP-13 by MT1-MMP was dependent on the C-terminal domain, as delta(249-451) proMMP-13, which lacks the haemopexin domain, and a chimaera from N-terminal MMP-13 and C-terminal MMP-19 (proMMP-13/19) were not processed by MT1-MMP expressing cells. Only the initial cleavage at Gly(35)-Ile(36) was dependent on MT1-MMP activity, as conversion to the active enzyme (Tyr(85) N-terminus) required a functional MMP-13 active site. Unlike proMMP-2 activation, this process was independent of tissue inhibitor of metalloproteinase-2 (TIMP-2) as MT1-MMP expressing cells from the TIMP-2-/- mouse efficiently activated proMMP-13.
authors.affiliation: School of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, UK. vk8@york.ac.uk
authors.forename: Vera
authors.initials: V
authors.lastname: Knäuper
authors.forename: Louise
authors.initials: L
authors.lastname: Bailey
authors.forename: Joanna R
authors.initials: JR
authors.lastname: Worley
authors.forename: Paul
authors.initials: P
authors.lastname: Soloway
authors.forename: Margaret L
authors.initials: ML
authors.lastname: Patterson
authors.forename: Gillian
authors.initials: G
authors.lastname: Murphy
mesh_terms: D000818:Animals; D002460:Cell Line; D017364:Collagenases / Q000737:chemistry* / Q000378:metabolism*; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000737:chemistry* / Q000378:metabolism*; D053509:Matrix Metalloproteinase 13; D053511:Matrix Metalloproteinase 14; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D017434:Protein Structure, Tertiary; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: D004792:Enzyme Precursors; C507096:Mmp14 protein, mouse; D019716:Tissue Inhibitor of Metalloproteinase-2; D017364:Collagenases; D053509:Matrix Metalloproteinase 13; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; C507081:Mmp13 protein, mouse; D053511:Matrix Metalloproteinase 14