Abstract
ADAM28, a member of a disintegrin and metalloproteinase (ADAM) family, has two isoforms, membrane-type form (ADAM28m) and secreted form (ADAM28s). Although ADAM28 is expressed and synthesized in a precursor form (proADAM28) by lymphocytes and some cancer cells, its activation mechanism and substrates remain unclear. Here, we report that proADAM28s of 65kDa is processed with active matrix metalloproteinase-7 (MMP-7) to 42- and 40-kDa forms which corresponds to active ADAM28s without propeptide. Processed ADAM28s digested insulin-like growth factor binding protein-3 (IGFBP-3) in both free and complex forms with IGF-I or IGF-II, and the digestion was prevented with EDTA, 1,10-phenanthroline, KB-R7785, tissue inhibitor of metalloproteinases-3 (TIMP-3), and TIMP-4. These data provide the first evidence that proADAM28s is activated by MMP-7 and ADAM28 digests IGFBP-3.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ADAM Proteins
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Enzyme Activation / drug effects
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Enzyme Precursors / genetics
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Enzyme Precursors / metabolism
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Humans
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Insulin-Like Growth Factor Binding Protein 3 / genetics
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Insulin-Like Growth Factor Binding Protein 3 / metabolism*
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Insulin-Like Growth Factor I / chemistry
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Insulin-Like Growth Factor I / metabolism
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Matrix Metalloproteinase 7 / metabolism*
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Metalloendopeptidases / antagonists & inhibitors
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Metalloendopeptidases / chemistry
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Metalloendopeptidases / genetics
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Metalloendopeptidases / metabolism*
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Protease Inhibitors / pharmacology
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Radioligand Assay
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Recombinant Proteins / antagonists & inhibitors
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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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Tissue Inhibitor of Metalloproteinases / pharmacology
Substances
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Enzyme Precursors
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Insulin-Like Growth Factor Binding Protein 3
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Protease Inhibitors
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Recombinant Proteins
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Tissue Inhibitor of Metalloproteinases
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Insulin-Like Growth Factor I
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ADAM Proteins
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ADAM28 protein, human
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Metalloendopeptidases
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Matrix Metalloproteinase 7