FIBROBLAST AND NEUTROPHIL COLLAGENASES CLEAVE AT 2 SITES IN THE CARTILAGE AGGRECAN INTERGLOBULAR DOMAIN

FOSANG AJ, LAST K, KNAUPER V, NEAME PJ, MURPHY G, HARDINGHAM TE, Tschesche H, HAMILTON JA (1993)
BIOCHEMICAL JOURNAL 295: 273-276.

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Zeitschriftenaufsatz | Veröffentlicht | Englisch
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Abstract / Bemerkung
The actions of recombinant human fibroblast collagenase (MMP1), purified polymorphonuclear leucocyte collagenase (MMP8) and their N-terminal catalytic domain fragments against cartilage aggrecan and an aggrecan GI-G2 fragment have been investigated in vitro. After activation with recombinant human stromelysin and trypsin, both collagenases were able to degrade human and porcine aggrecans to a similar extent. An N-terminal G1-G2 fragment (150 kDa) was used to identify specific cleavage sites occurring within the proteinase-sensitive interglobular domain between G1 and G2. Two specific sites were found; one at an Asn341-Phe342 bond and another at Asp441-Leu442 (human sequence). This specificity of the collagenases for aggrecan G1-G2 was identical with that of the truncated metalloproteinase matrilysin (MMP7), but different from those of stromelysin (MMP3) and the gelatinases (MMP2 or gelatinase A; MMP9 or gelatinase B) which cleave at the Asn-Phe site, but not the Asp-Leu site. In addition, collagenase catalytic fragments lacking C-terminal hemopexin-like domains were tested and shown to exhibit the same specificities for the G1-G2 fragment as the full-length enzymes. Thus the specificity of the collagenases for cartilage aggrecan was not influenced by the presence or absence of the C-terminal domain. Together with our previous findings, the results show that stromelysin-1, matrilysin, gelatinases A and B and fibroblast and neutrophil collagenases cleave at a common, preferred site in the aggrecan interglobular domain, and additionally that both fibroblast and neutrophil collagenases cleave at a second site in the interglobular domain that is not available to stromelysin or gelatinases.
Erscheinungsjahr
Zeitschriftentitel
BIOCHEMICAL JOURNAL
Band
295
Seite
273-276
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PUB-ID

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FOSANG AJ, LAST K, KNAUPER V, et al. FIBROBLAST AND NEUTROPHIL COLLAGENASES CLEAVE AT 2 SITES IN THE CARTILAGE AGGRECAN INTERGLOBULAR DOMAIN. BIOCHEMICAL JOURNAL. 1993;295:273-276.
FOSANG, A. J., LAST, K., KNAUPER, V., NEAME, P. J., MURPHY, G., HARDINGHAM, T. E., Tschesche, H., et al. (1993). FIBROBLAST AND NEUTROPHIL COLLAGENASES CLEAVE AT 2 SITES IN THE CARTILAGE AGGRECAN INTERGLOBULAR DOMAIN. BIOCHEMICAL JOURNAL, 295, 273-276.
FOSANG, A. J., LAST, K., KNAUPER, V., NEAME, P. J., MURPHY, G., HARDINGHAM, T. E., Tschesche, H., and HAMILTON, J. A. (1993). FIBROBLAST AND NEUTROPHIL COLLAGENASES CLEAVE AT 2 SITES IN THE CARTILAGE AGGRECAN INTERGLOBULAR DOMAIN. BIOCHEMICAL JOURNAL 295, 273-276.
FOSANG, A.J., et al., 1993. FIBROBLAST AND NEUTROPHIL COLLAGENASES CLEAVE AT 2 SITES IN THE CARTILAGE AGGRECAN INTERGLOBULAR DOMAIN. BIOCHEMICAL JOURNAL, 295, p 273-276.
A.J. FOSANG, et al., “FIBROBLAST AND NEUTROPHIL COLLAGENASES CLEAVE AT 2 SITES IN THE CARTILAGE AGGRECAN INTERGLOBULAR DOMAIN”, BIOCHEMICAL JOURNAL, vol. 295, 1993, pp. 273-276.
FOSANG, A.J., LAST, K., KNAUPER, V., NEAME, P.J., MURPHY, G., HARDINGHAM, T.E., Tschesche, H., HAMILTON, J.A.: FIBROBLAST AND NEUTROPHIL COLLAGENASES CLEAVE AT 2 SITES IN THE CARTILAGE AGGRECAN INTERGLOBULAR DOMAIN. BIOCHEMICAL JOURNAL. 295, 273-276 (1993).
FOSANG, AJ, LAST, K, KNAUPER, V, NEAME, PJ, MURPHY, G, HARDINGHAM, TE, Tschesche, Harald, and HAMILTON, JA. “FIBROBLAST AND NEUTROPHIL COLLAGENASES CLEAVE AT 2 SITES IN THE CARTILAGE AGGRECAN INTERGLOBULAR DOMAIN”. BIOCHEMICAL JOURNAL 295 (1993): 273-276.

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Quantification of a matrix metalloproteinase-generated aggrecan G1 fragment using monospecific anti-peptide serum.
Lark MW, Williams H, Hoernner LA, Weidner J, Ayala JM, Harper CF, Christen A, Olszewski J, Konteatis Z, Webber R., Biochem J 307 ( Pt 1)(), 1995
PMID: 7717983
VDIPEN, a metalloproteinase-generated neoepitope, is induced and immunolocalized in articular cartilage during inflammatory arthritis.
Singer II, Kawka DW, Bayne EK, Donatelli SA, Weidner JR, Williams HR, Ayala JM, Mumford RA, Lark MW, Glant TT., J Clin Invest 95(5), 1995
PMID: 7537757
Neutrophil collagenase (MMP-8) cleaves at the aggrecanase site E373-A374 in the interglobular domain of cartilage aggrecan.
Fosang AJ, Last K, Neame PJ, Murphy G, Knäuper V, Tschesche H, Hughes CE, Caterson B, Hardingham TE., Biochem J 304 ( Pt 2)(), 1994
PMID: 7998967

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