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.
English
W R
WR
School of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, UK. w.english@uea.ac.uk
Velasco
G
G
Stracke
J O
JO
Knäuper
V
V
Murphy
G
G
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