RECK Forms Cowbell-shaped Dimers and Inhibits Matrix Metalloproteinase-catalyzed Cleavage of Fibronectin
RECK Forms Cowbell-shaped Dimers and Inhibits Matrix Metalloproteinase-catalyzed Cleavage of Fibronectin
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DOI：
10.1074/jbc.m806212200
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发表时间：
2009-02-06
影响因子：
4.8
通讯作者：
Noda, Makoto
中科院分区：
文献类型：
--
作者：
Omura, Akira;Matsuzaki, Tomoko;Noda, Makoto
RECK是一种膜锚定蛋白酶调节因子，在哺乳动物的发育和肿瘤抑制中起着重要作用。然而，这些生物活性的生化基础仍然知之甚少。在这里，我们报告的重组RECK蛋白在小鼠成纤维细胞中表达和纯化到接近同质性的属性。多条证据表明RECK形成二聚体。使用透射电子显微镜的单粒子重建揭示了一个独特的牛铃状形状的RECK二聚体。RECK被MMP-2和MMP-7切割，并竞争性抑制MMP-7催化的纤连蛋白切割。在内源性RECK表达最小的HT 1080细胞中强制RECK表达导致与细胞相关的纤连蛋白量增加。我们的数据表明，RECK保护纤连蛋白免受MMP介导的降解的能力。
The membrane-anchored protease regulator RECK plays important roles in mammalian development and tumor suppression. The biochemical bases of these bioactivities, however, remain poorly understood. Here we report on the properties of a recombinant RECK protein expressed in mouse fibroblasts and purified to near homogeneity. Multiple lines of evidence indicate that RECK forms dimers. Single particle reconstruction using transmission electron microscopy revealed a unique cowbell-like shaped RECK dimer. RECK is cleaved by MMP-2 and MMP-7 and competitively inhibits MMP-7-catalyzed cleavage of fibronectin. Forced RECK expression in HT1080 cells, whose endogenous RECK expression is minimal, leads to an increase in the amount of fibronectin associated with the cell. Our data demonstrate the ability of RECK to protect fibronectin from MMP-mediated degradation.