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Tissue inhibitor of metalloproteinase (TIMP-2). A new member of the metalloproteinase inhibitor family.

Abstract
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.
AuthorsW G Stetler-Stevenson, H C Krutzsch, L A Liotta
JournalThe Journal of biological chemistry (J Biol Chem) Vol. 264 Issue 29 Pg. 17374-8 (Oct 15 1989) ISSN: 0021-9258 [Print] United States
PMID2793861 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Amino Acids
  • Neoplasm Proteins
  • Tissue Inhibitor of Metalloproteinase-2
  • Metalloendopeptidases
Topics
  • Amino Acid Sequence
  • Amino Acids (analysis)
  • Chromatography
  • Humans
  • Melanoma (metabolism)
  • Metalloendopeptidases (antagonists & inhibitors)
  • Molecular Sequence Data
  • Neoplasm Proteins (isolation & purification, pharmacology)
  • Sequence Homology, Nucleic Acid
  • Tissue Inhibitor of Metalloproteinase-2
  • Tumor Cells, Cultured

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