INTERACTION OF THE SMALL INTERSTITIAL PROTEOGLYCANS BIGLYCAN, DECORIN AND FIBROMODULIN WITH TRANSFORMING GROWTH-FACTOR-BETA
INTERACTION OF THE SMALL INTERSTITIAL PROTEOGLYCANS BIGLYCAN, DECORIN AND FIBROMODULIN WITH TRANSFORMING GROWTH-FACTOR-BETA
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DOI：
10.1042/bj3020527
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发表时间：
1994-09-01
影响因子：
4.1
通讯作者：
RUOSLAHTI, E
中科院分区：
文献类型：
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作者：
HILDEBRAND, A;ROMARIS, M;RUOSLAHTI, E
我们分析了核心蛋白聚糖家族的三种蛋白聚糖，核心蛋白聚糖，双糖链蛋白聚糖和纤调蛋白与转化生长因子β（TGF-β）的相互作用。从人cDNA表达的蛋白聚糖核心蛋白作为与大肠杆菌麦芽糖结合蛋白的融合蛋白，各自结合TGF-β 1。它们与其他几种生长因子的结合可以忽略不计。从牛组织中分离的完整核心蛋白聚糖、双糖链蛋白聚糖和纤调蛋白与融合蛋白竞争TGF-β结合。亲和力测量表明，一个两个网站的结合模型与Kd值范围为1至20 nM的高亲和力结合位点和50至200 nM的低亲和力结合位点。化学计量表明，高亲和力结合位点存在于10个蛋白聚糖核心分子之一中，并且每个分子含有低亲和力结合位点。与纤调蛋白或非糖基化融合蛋白相比，组织来源的双糖链蛋白聚糖和核心蛋白聚糖是TGF-β结合的较不有效的竞争者;去除核心蛋白聚糖和双糖链蛋白聚糖的软骨素/硫酸皮肤素链（纤调蛋白是硫酸角质素蛋白聚糖）增加了核心蛋白聚糖和双糖链蛋白聚糖的活性，表明糖胺聚糖链可能阻碍核心蛋白与TGF-β的相互作用。融合蛋白竞争放射性标记的TGF-β与Mv 1 Lu细胞和内皮细胞的结合。亲和标记显示TGF-β与β聚糖和Mv 1 Lu细胞中的I型受体以及内皮细胞中的内皮糖蛋白的结合减少，但与II型受体的结合不受影响。TGF-β 2和TGF-β 3也与所有三种融合蛋白结合。潜在的重组TGF-β 1前体与纤调蛋白轻微结合，而与核心蛋白聚糖和双糖链蛋白聚糖完全不结合。结果显示，三种核心蛋白聚糖型蛋白聚糖各自结合TGF-β同种型，并且它们的结合性质存在轻微差异。它们可以通过将TGF-β隔离到细胞外基质中来调节TGF-β活性。
We have analysed the interactions of three proteoglycans of the decorin family, decorin, biglycan and fibromodulin, with transforming growth factor beta (TGF-beta). The proteoglycan core proteins, expressed from human cDNAs as fusion proteins with Escherichia coli maltose-binding protein, each bound TGF-beta 1. They showed only negligible binding to several other growth factors. Intact decorin, biglycan and fibromodulin isolated from bovine tissues competed with the fusion proteins for the TGF-beta binding. Affinity measurements suggest a two-site binding model with K-d values ranging from 1 to 20 nM for a high-affinity binding site and 50 to 200 nM for the lower-affinity binding site. The stoichiometry indicated that the high-affinity binding site was present in one of ten proteoglycan core molecules and that each molecule contained a low-affinity binding site. Tissue-derived biglycan and decorin were less effective competitors for TGF-beta binding than fibromodulin or the non-glycosylated fusion proteins; removal of the chondroitin/dermatan sulphate chains of decorin and biglycan (fibromodulin is a keratan sulphate proteoglycan) increased the activities of decorin and biglycan, suggesting that the glycosaminoglycan chains may hinder the interaction of the core proteins with TGF-beta. The fusion proteins competed for the binding of radiolabelled TGF-beta to Mv 1 Lu cells and endothelial cells. Affinity labelling showed that the binding of TGF-beta to betaglycan and the type-I receptors in Mv 1 Lu cells and to endoglin in endothelial cells was reduced, but the binding to the type-II receptors was unaffected. TGF-beta 2 and 3 also bound to all three fusion proteins. Latent recombinant TGF-beta 1 precursor bound slightly to fibromodulin and not at all to decorin and biglycan. The results show that the three decorin-type proteoglycans each bind TGF-beta isoforms and that slight differences exist in their binding properties. They may regulate TGF-beta activities by sequestering TGF-beta into extracellular matrix.