title: Meprins process matrix metalloproteinase-9 (MMP-9)/gelatinase B and enhance the activation kinetics by MMP-3.
abstract: Meprin α and β, members of the astacin family of zinc metalloproteinases, are unique plasma membrane and secreted proteases known to cleave a wide range of biological substrates involved in inflammation, cancer and fibrosis. In this study, we identified proMMP-9 as a novel substrate and show that aminoterminal meprin-mediated clipping improves the activation kinetics of proMMP-9 by MMP-3, an efficient activator of proMMP-9. Interestingly, the NH(2)-terminus LVLFPGDL, generated by incubation with meprin α, is identical to the form produced in conditioned media from human neutrophils and monocytes. Hence, this meprin-mediated processing and enhancement of MMP-9 activation kinetics may have biological relevance in the context of in vivo inflammatory processes.
authors.affiliation: Laboratory of Immunobiology, Rega Institute for Medical Research, University of Leuven, Minderbroedersstraat 10, 3000 Leuven, Belgium.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Geurts
authors.forename: Christoph
authors.initials: C
authors.lastname: Becker-Pauly
authors.forename: Erik
authors.initials: E
authors.lastname: Martens
authors.forename: Paul
authors.initials: P
authors.lastname: Proost
authors.forename: Philippe E
authors.initials: PE
authors.lastname: Van den Steen
authors.forename: Walter
authors.initials: W
authors.lastname: Stöcker
authors.forename: Ghislain
authors.initials: G
authors.lastname: Opdenakker
mesh_terms: D000595:Amino Acid Sequence; D002478:Cells, Cultured / Q000378:metabolism; D017077:Culture Media, Conditioned; D006801:Humans; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008969:Molecular Sequence Data; D009000:Monocytes / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D008625:Tiopronin / Q000378:metabolism*
chemical_list: D017077:Culture Media, Conditioned; D008625:Tiopronin; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9