Abstract
Soluble proenzyme forms of the catalytic domains of membrane-type matrix metalloproteinases 1 and 2 (MT1-MMP and MT2-MMP) and a form of MT1-MMP containing the catalytic and hemopexin domains were expressed as soluble recombinant proteins. Purified, activated forms of the MT-MMP were shown to degrade fibronectin, tenascin, nidogen, aggrecan and perlecan. Only MT2-MMP showed activity against laminin. MT1-MMP retaining the hemopexin domain was able to specifically cleave native type-I and type-III collagens into the 3/4-1/4 fragments typical of the specific collagenases. The catalytic domain alone did not retain this activity. The MT-MMP did not degrade interleukin-1beta, but, similarly to many other MMP, could process a pro [tumor necrosis factor (TNF) alpha] fusion protein to release mature TNF. However, the latter was subsequently degraded into smaller fragments. These results demonstrate that, in addition to their ability to activate other MMP, such as progelatinase A/proMMP2 and procollagenase-3/proMMP13, MT-MMP degrade a number of extracellular matrix macromolecules. Their location at the surface of cells implies that they could play a significant role in the modulation of cell-matrix interactions.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aggrecans
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Blotting, Western
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Collagen / metabolism
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Collagenases / chemistry
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Collagenases / metabolism*
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Electrophoresis, Polyacrylamide Gel
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Enzyme Activation / physiology
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Escherichia coli / genetics
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Extracellular Matrix / chemistry
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Extracellular Matrix / metabolism
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Extracellular Matrix Proteins*
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Fibronectins / metabolism
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Gelatinases / chemistry
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Gelatinases / metabolism*
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Heparan Sulfate Proteoglycans*
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Heparitin Sulfate / metabolism
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Humans
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Interleukin-1 / metabolism
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Laminin / metabolism
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Lectins, C-Type
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Matrix Metalloproteinase 1
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Matrix Metalloproteinase 2
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Membrane Glycoproteins / metabolism
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Metalloendopeptidases / chemistry
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Metalloendopeptidases / metabolism*
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Peptide Fragments / metabolism
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Proteoglycans / metabolism
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Recombinant Proteins / chemistry
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Substrate Specificity
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Tenascin / metabolism
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Aggrecans
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Extracellular Matrix Proteins
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Fibronectins
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Heparan Sulfate Proteoglycans
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Interleukin-1
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Laminin
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Lectins, C-Type
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Membrane Glycoproteins
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Peptide Fragments
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Proteoglycans
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Recombinant Proteins
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Tenascin
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Tumor Necrosis Factor-alpha
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nidogen
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perlecan
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Collagen
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Heparitin Sulfate
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Collagenases
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Gelatinases
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Metalloendopeptidases
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Matrix Metalloproteinase 2
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Matrix Metalloproteinase 1