title: Primary structure and function of stromelysin/transin in cartilage matrix turnover.
abstract: Stromelysin/Transin is a member of the matrix metalloprotease gene family. This metalloprotease is synthesized as a preproenzyme with a predicted size of 53,977 Da including a 17 amino acid signal peptide. Prostromelysin is secreted from normal and transformed cells in two forms with apparent molecular masses on NaDodSO4 gels of 60 and 58-kDa. The minor 60-kDa species contains N-linked oligosaccharide(s). Stromelysin consists of three domains the amino terminal propeptide(s) domain contains the tribasic amino acid sequence RRK which is important in the proteolytic activation of this zymogen by trypsin-like serine proteases. The second domain consists of the catalytic domain which contains the zinc binding site. The carboxyl-terminal hemopexin domain has no known function and can be removed without a loss of enzymatic activity. Stromelysin has a broad range of substrate specificity including proteoglycans, casein, fibronectin, laminin, native type IV and IX collagen and gelatin but not type I collagen. In the presence of trypsin or plasmin, catalytic amounts of this enzyme can also fully activate interstitial fibroblast collagenase. We have developed a panel of monoclonal antibodies against stromelysin which will be useful for the tissue localization of the various species of this enzyme in tissues. In addition, we have demonstrated that either human rIL-1 (alpha) or rTNF (alpha) can stimulate the expression of this enzyme in cultured bovine articular cartilage at least 10-fold. Based on western blot analysis, the zymogen form of the enzyme was the major enzyme species detected in either the media or cartilage matrix compartments of cytokine treated cultures.
authors: Institute for Arthritis and Autoimmunity, Miles Research Center, West Haven, CT 06516.
authors: S M
authors: SM
authors: Wilhelm
authors: D
authors: D
authors: Wunderlich
authors: C A
authors: CA
authors: Maniglia
authors: A Z
authors: AZ
authors: Eisen
authors: G I
authors: GI
authors: Goldberg
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001665:Binding Sites; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D002417:Cattle; D004790:Enzyme Induction / Q000187:drug effects; D005109:Extracellular Matrix / Q000378:metabolism*; D007074:Immunoglobulin G / Q000276:immunology; D007375:Interleukin-1 / Q000494:pharmacology; D019278:Matrix Metalloproteinase 3; D008666:Metalloendopeptidases / Q000737:chemistry* / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009924:Organ Culture Techniques; D021382:Protein Sorting Signals; D013379:Substrate Specificity; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015032:Zinc / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D007375:Interleukin-1; D021382:Protein Sorting Signals; D014409:Tumor Necrosis Factor-alpha; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3; D015032:Zinc