Membrane-type 1 MMP (MMP-14) cleaves at three sites in the aggrecan interglobular domain

被引:47
作者
Fosang, AJ [1 ]
Last, K
Fujii, Y
Seiki, M
Okada, Y
机构
[1] Univ Melbourne, Royal Childrens Hosp, Dept Paediat, Orthopaed Mol Biol Unit, Parkville, Vic 3052, Australia
[2] Fukui Med Univ, Dept Chem, Fukui 9101193, Japan
[3] Univ Tokyo, Inst Med Sci, Dept Canc Res, Minato Ku, Tokyo 1080071, Japan
[4] Keio Univ, Sch Med, Dept Pathol, Shinjuku Ku, Tokyo 1600016, Japan
基金
英国医学研究理事会;
关键词
matrix metalloproteinase; membrane-type matrix metalloproteinase; aggrecan; neo-epitope; arthritis;
D O I
10.1016/S0014-5793(98)00667-X
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
An aggrecan G1-G2 substrate was used to determine sites within the interglobular domain that were susceptible to cleavage by MT1-MMP. Degradation products were identified by Western blotting with neo-epitope antibodies specific for MMP-derived N- and C-terminal sequences, The results showed that MT1-MMP cleaved at the N-341-F-342 and D-441-L-442 bonds, as shown for other MMPs, and also at a site 13 amino acids C-terminal to the N-341-F-342 site. The G2 product of this additional cleavage was identified by sequence analysis and revealed an N-terminus commencing T(355)VxxPDVELPLP. The data are consistent with MT1-MMP cleavage at three sites in the aggrecan interglobular domain; one at N-342-F-342, a second at D-441-L-442 and a third at Q(354)-T-355. (C) 1998 Federation of European Biochemical Societies.
引用
收藏
页码:186 / 190
页数:5
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