Catalytic activities of membrane-type 6 matrix metalloproteinase (MMP25).
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.
School of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, UK. w.english@uea.ac.uk
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English
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Velasco
J O
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Stracke
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Knäuper
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Murphy
D000911:Antibodies, Monoclonal; D015153:Blotting, Western; D020134:Catalytic Domain; D004591:Electrophoresis, Polyacrylamide Gel; D005109:Extracellular Matrix / Q000201:enzymology / Q000378:metabolism*; D058851:GPI-Linked Proteins; D006801:Humans; D006868:Hydrolysis; D019278:Matrix Metalloproteinase 3 / Q000737:chemistry / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000737:chemistry / Q000378:metabolism*; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000737:chemistry / Q000378:metabolism; D017510:Protein Folding; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013379:Substrate Specificity
D000911:Antibodies, Monoclonal; D058851:GPI-Linked Proteins; D061965:Matrix Metalloproteinase Inhibitors; D011994:Recombinant Proteins; C402225:MMP17 protein, human; D020782:Matrix Metalloproteinases; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; C403928:matrix metalloproteinase 25; D019278:Matrix Metalloproteinase 3