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: Nathalie Geurts, Christoph Becker-Pauly, Erik Martens, Paul Proost, Philippe E Van den Steen, Walter Stöcker, Ghislain Opdenakker
• Journal: FEBS letters (FEBS Lett) Vol. 586 Issue 24 Pg. 4264-9 (Dec 14 2012) ISSN: 1873-3468 [Electronic] England
• PMID: 23123160 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Chemical References

• Culture Media, Conditioned
• Tiopronin
• MMP3 protein, human
• Matrix Metalloproteinase 3
• Matrix Metalloproteinase 9

Topics

• Amino Acid Sequence
• Cells, Cultured (metabolism)
• Culture Media, Conditioned
• Humans
• Matrix Metalloproteinase 3 (metabolism)
• Matrix Metalloproteinase 9 (metabolism)
• Molecular Sequence Data
• Monocytes (metabolism)
• Neutrophils (metabolism)
• Tiopronin (metabolism)