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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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.
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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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