Abstract
Among the five membrane-type matrix metalloproteinases (MT-MMPs), MT1-, MT2-, MT3-, and MT5-MMPs have about a 20-amino acid cytoplasmic tail following the transmembrane domain. In contrast, a putative transmembrane domain of MT4-MMP locates at the very C-terminal end, and the expected cytoplasmic tail is very short or nonexistent. Such sequences often act as a glycosylphosphatidylinositol (GPI) anchoring signal rather than as a transmembrane domain. We thus examined the possibility that MT4-MMP is a GPI-anchored proteinase. Our results showed that [(3)H]ethanolamine, which can be incorporated into the GPI unit, specifically labeled the MT4-MMP C-terminal end in a sequence-dependent manner. In addition, phosphatidylinositol-specific phospholipase C treatment released the MT4-MMP from the surface of transfected cells. These results indicate that MT4-MMP is the first GPI-anchored proteinase in the MMP family. During cultivation of the transfected cells, MT4-MMP appeared to be shed from the cell surface by the action of an endogenous metalloproteinase. GPI anchoring of MT4-MMP on the cell surface indicates a unique biological function and character for this proteinase.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Binding Sites
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CHO Cells
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COS Cells
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Chlorocebus aethiops
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Cricetinae
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Cricetulus
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Endopeptidases / drug effects
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Endopeptidases / metabolism
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Ethanolamine / metabolism
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Fluorescent Antibody Technique, Indirect
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Glycosylphosphatidylinositols / metabolism*
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Humans
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Matrix Metalloproteinases / chemistry
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Matrix Metalloproteinases / genetics
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Matrix Metalloproteinases / metabolism*
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Matrix Metalloproteinases, Membrane-Associated
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Metalloendopeptidases*
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Mice
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Microscopy, Confocal
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Molecular Sequence Data
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Phenylalanine / analogs & derivatives
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Phenylalanine / pharmacology
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Phosphatidylinositol Diacylglycerol-Lyase
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Phosphoinositide Phospholipase C
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Protease Inhibitors / pharmacology
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Recombinant Fusion Proteins / analysis
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Recombinant Fusion Proteins / genetics
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Sequence Alignment
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Thiophenes / pharmacology
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Tritium
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Type C Phospholipases / pharmacology
Substances
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Glycosylphosphatidylinositols
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Protease Inhibitors
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Recombinant Fusion Proteins
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Thiophenes
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Tritium
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Phenylalanine
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Ethanolamine
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batimastat
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Type C Phospholipases
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Phosphoinositide Phospholipase C
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Endopeptidases
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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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Mmp17 protein, mouse
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Phosphatidylinositol Diacylglycerol-Lyase