Tissue inhibitor of metalloproteinase (TIMP-2). A new member of the metalloproteinase inhibitor family.
Human melanoma cells secret a 21-kDa protein, termed CSC-21K, which binds with 1:1 molar stoichiometry to the matrix metalloproteinase type IV collagenase proenzyme (70-kDa gelatinase) secreted by the same cells. This binding protein has been purified and its complete primary structure determined by sequencing overlapping peptides which span the entire protein. The amino acid sequence demonstrates that this protein shares significant homology with human TIMP (tissue inhibitor of metalloproteinase), including conservation of the positions of the 12 cysteine residues and 3 of 4 tryptophan residues. The identification of CSC-21K now indicates that a family of TIMP-related proteins exists. Individual members of this family may possess selective affinities for different members of the matrix metalloproteinase family. CSC-21K produced by tumor cells is isolated as a 1:1 molar complex with type IV procollagenase, as demonstrated by amino acid composition analysis. Addition of purified CSC-21K to the activated metalloproteinase results in inhibition of the collagenolytic activity in a stoichiometric fashion. Based on its sequence homology to TIMP and ability to inhibit type IV collagenolysis we propose the name TIMP-2 for this inhibitor.
Stetler-Stevenson
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WG
Tumor Invasion and Metastasis Section, Laboratory of Pathology, National Cancer Institute, Bethesda, Maryland 20892.
Krutzsch
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HC
Liotta
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LA
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis; D002845:Chromatography; D006801:Humans; D008545:Melanoma / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000302:isolation & purification / Q000494:pharmacology; D012689:Sequence Homology, Nucleic Acid; D019716:Tissue Inhibitor of Metalloproteinase-2; D014407:Tumor Cells, Cultured
D000596:Amino Acids; D009363:Neoplasm Proteins; D019716:Tissue Inhibitor of Metalloproteinase-2; D008666:Metalloendopeptidases