Billington C J, Clark I M, Cawston T E
Department of Rheumatology, School of Clinical and Medical Sciences, University of Newcastle, Newcastle upon Tyne NE2 4HH, UK.
Biochem J. 1998 Nov 15;336 ( Pt 1)(Pt 1):207-12. doi: 10.1042/bj3360207.
The breakdown of aggrecan in cartilage is, in part, mediated by an enzyme named aggrecanase that cleaves within the interglobular domain of the molecule between a glutamic residue and an alanine residue. Although the enzyme cleavage site has been identified, the identity, characteristics and localization of this enzyme remain unclear. We have demonstrated that membranes isolated from stimulated chondrocytes are able to generate aggrecan fragments that are labelled by an antibody that recognizes the new N-terminus formed by aggrecanase activity. It was further shown that the membrane activity was a metalloproteinase but was not inhibited by the naturally occurring matrix metalloproteinase (MMP) inhibitors, TIMPs 1 and 2. These results show that an aggrecanase activity is associated with the membranes of the chondrocytes and is a metalloproteinase, but might not be a member of the MMP family.
软骨中聚集蛋白聚糖的降解部分是由一种名为聚集蛋白聚糖酶的酶介导的,该酶在分子的球间结构域内谷氨酸残基和丙氨酸残基之间进行切割。尽管已经确定了该酶的切割位点,但这种酶的身份、特性和定位仍不清楚。我们已经证明,从受刺激的软骨细胞中分离出的膜能够产生聚集蛋白聚糖片段,这些片段可被识别由聚集蛋白聚糖酶活性形成的新N端的抗体标记。进一步表明,膜活性是一种金属蛋白酶,但不受天然存在的基质金属蛋白酶(MMP)抑制剂TIMP 1和TIMP 2的抑制。这些结果表明,聚集蛋白聚糖酶活性与软骨细胞膜相关,是一种金属蛋白酶,但可能不是MMP家族的成员。