Synthetic emmprin peptides with chitobiose substitution stimulate MMP-2 production by fibroblasts.
Synthetic emmprin peptides with chitobiose substitution stimulate MMP-2 production by fibroblasts.
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DOI：
10.1186/1471-2407-11-300
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发表时间：
2011-07-17
期刊：
影响因子：
3.8
通讯作者：
Nabeshima K
中科院分区：
文献类型：
--
作者：
Kawakami T;Sameshima T;Hojo H;Koga K;Nakahara Y;Toole BP;Suzumiya J;Okada Y;Iwasaki A;Nabeshima K
Emmprin是一种含有两个Ig结构域的糖蛋白，富含在肿瘤细胞表面，并刺激相邻基质细胞产生基质金属蛋白酶(MMPs)。它的第一个Ig结构域(ECI)包含生物活性部位。Emmprin的活性依赖于N-糖基化是有争议的。我们研究了含有最短糖的合成ECI是否具有功能活性。用硫代酯法合成完整的含有糖链的ECI多肽，即壳二糖单元或N-连接的核心五糖，并将其加入成纤维细胞中，以检测它们是否刺激基质金属蛋白酶-2的产生。携带壳二糖单位的ECI-(GlcNAc)2，而不含壳二糖单位的ECI或单独携带壳二糖单位的ECI可剂量依赖性地刺激成纤维细胞产生基质金属蛋白酶-2。具有较长壳二糖单元的ECI-[(Man)3(GlcNAc)2]也能刺激基质金属蛋白酶-2的产生，但其刺激程度低于ECI-(GlcNAc)2。我们的结果表明，当用N-糖基化的二糖取代ECI-[(Man)3(GlcNAc)2]时，ECI可以模拟Emmprin的活性。
Emmprin, a glycoprotein containing two Ig domains, is enriched on tumor cell surfaces and stimulates matrix metalloproteinase (MMP) production by adjacent stromal cells. Its first Ig domain (ECI) contains the biologically active site. The dependence of emmprin activity on N-glycosylation is controversial. We investigated whether synthetic ECI with the shortest sugar is functionally active. The whole ECI peptides carrying sugar chains, a chitobiose unit or N-linked core pentasaccharide, were synthesized by the thioester method and added to fibroblasts to examine whether they stimulate MMP-2 production. ECI carrying a chitobiose unit, ECI-(GlcNAc) 2, but not ECI without a chitobiose unit or the chitobiose unit alone, dose-dependently stimulated MMP-2 production by fibroblasts. ECI with longer chitobiose units, ECI-[(Man)3(GlcNAc)2], also stimulated MMP-2 production, but the extent of its stimulation was lower than that of ECI-(GlcNAc)2. Our results indicate that ECI can mimic emmprin activity when substituted with chitobiose, the disaccharide with which N-glycosylation starts.
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影响因子：
7.3
作者：
Nabeshima, K;Suzumiya, J;Kikuchi, M
通讯作者：
Kikuchi, M
影响因子：
3.2
作者：
Polette, M;Gilles, C;Birembaut, P
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Birembaut, P
影响因子：
4.8
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Toole, BP
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3.4
作者：
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STAMP, GWH
影响因子：
4.8
作者：
Berditchevski, F;Chang, S;Hemler, ME
通讯作者：
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