Abstract
This study describes the biochemical characterisation of the catalytic domain of membrane-type 6 matrix metalloproteinase (MT6-MMP, MMP25, leukolysin). Its activity towards synthetic peptide substrates, components of the extracellular matrix and inhibitors of MMPs was studied and compared with MT1-MMP, MT4-MMP and stromelysin-1. We have found that MT6-MMP is closer in function to stromelysin-1 than MT1 and MT4-MMP in terms of substrate and inhibitor specificity, being able to cleave type-IV collagen, gelatin, fibronectin and fibrin. However, it differs from stromelysin-1 and MT1-MMP in its inability to cleave laminin-I, and unlike stromelysin-1 cannot activate progelatinase B. Our findings suggest that MT6-MMP could play a role in cellular migration and invasion of the extracellular matrix and basement membranes and its activity may be tightly regulated by all members of the TIMP family.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antibodies, Monoclonal
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Blotting, Western
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Catalytic Domain
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Electrophoresis, Polyacrylamide Gel
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Extracellular Matrix / enzymology
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Extracellular Matrix / metabolism*
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GPI-Linked Proteins
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Humans
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Hydrolysis
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Matrix Metalloproteinase 3 / chemistry
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Matrix Metalloproteinase 3 / metabolism
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Matrix Metalloproteinase Inhibitors
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Matrix Metalloproteinases / chemistry
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Matrix Metalloproteinases / metabolism*
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Matrix Metalloproteinases, Membrane-Associated
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Metalloendopeptidases / chemistry
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Metalloendopeptidases / metabolism
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Protein Folding
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Recombinant Proteins / chemistry
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Recombinant Proteins / metabolism
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Substrate Specificity
Substances
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Antibodies, Monoclonal
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GPI-Linked Proteins
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Matrix Metalloproteinase Inhibitors
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Recombinant Proteins
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MMP17 protein, human
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Matrix Metalloproteinases
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Matrix Metalloproteinases, Membrane-Associated
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Metalloendopeptidases
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matrix metalloproteinase 25
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Matrix Metalloproteinase 3