Chondroitin sulfate chains on syndecan-1 and syndecan-4 from normal murine mammary gland epithelial cells are structurally and functionally distinct and cooperate with heparan sulfate chains to bind growth factors - A novel function to control binding of midkine, pleiotrophin, and basic fibroblast growth factor
Chondroitin sulfate chains on syndecan-1 and syndecan-4 from normal murine mammary gland epithelial cells are structurally and functionally distinct and cooperate with heparan sulfate chains to bind growth factors - A novel function to control binding of midkine, pleiotrophin, and basic fibroblast growth factor
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DOI：
10.1074/jbc.m403031200
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发表时间：
2004-09-03
影响因子：
4.8
通讯作者：
Sugahara, K
中科院分区：
文献类型：
--
作者：
Deepa, SS;Yamada, S;Sugahara, K
对正常鼠乳腺上皮细胞同时合成的混合型跨膜蛋白聚糖syndecan-1和-4胞外域的硫酸乙酰肝素(HS)和硫酸软骨素(CS)链进行了比较分析。尽管 HS 链在结构上无法区分，但有趣的是，CS 链在结构和功能上不同，这可能反映了参与 HS 和 CS 合成的磺基转移酶的差异调节。两种多聚糖的CS链包含非硫酸化、4-O-、6-O-和4,6-O-二硫酸化N-乙酰半乳糖胺的二糖单元，并且显着不同，多聚糖4的硫酸化程度更高。使用 BIAcore 系统的功能分析表明，碱性成纤维细胞生长因子 (bFGF) 仅与两种多配体的 HS 链特异性结合，而中期因子 (MK) 和多效素 (PTN) 不仅与 HS 结合，还与 CS 链结合。与 syndecan-1 相比，MK 和 PTN 与 syndecan-4 的 CS 链的结合更强，这支持了结构和功能差异。有趣的是，去除CS链降低了两种多聚糖的MK、PTN和bFGF的缔合和解离速率常数，表明这些生长因子同时结合到两种类型的链上，产生三元复合物，与单独的HS链相比，该复合物能够更有效地将生长因子转移到相应的细胞表面受体。 MK 和 PTN 与 syndecan-1 的结合也显示了核心蛋白的参与，这表明在这些生长因子的结合及其递送至细胞表面受体中与 HS 和/或 CS 链合作的可能性。
A comparative analysis was carried out of heparan sulfate (HS) and chondroitin sulfate ( CS) chains of the ectodomains of hybrid type transmembrane proteoglycans, syndecan-1 and -4, synthesized simultaneously by normal murine mammary gland epithelial cells. Although the HS chains were structurally indistinguishable, intriguingly the CS chains were structurally and functionally distinct, probably reflecting the differential regulation of sulfotransferases involved in the synthesis of HS and CS. The CS chains of the two syndecans comprised nonsulfated, 4-O-, 6-O-, and 4,6-O- disulfated N-acetylgalactosamine- containing disaccharide units and were significantly different, with a higher degree of sulfation for syndecan-4. Functional analysis using a BIAcore system showed that basic fibroblast growth factor ( bFGF) specifically bound only to the HS chains of both syndecans, whereas midkine (MK) and pleiotrophin (PTN) bound not only to the HS but also to the CS chains. Stronger binding of MK and PTN to the CS chains of syndecan- 4 than those of syndecan- 1 was revealed, supporting the structural and functional differences. Intriguingly, removal of the CS chains decreased the association and dissociation rate constants of MK, PTN, and bFGF for both syndecans, suggesting the simultaneous binding of these growth factors to both types of chains, producing a ternary complex that transfers the growth factors to the corresponding cell surface receptors more efficiently compared with the HS chains alone. The involvement of the core protein was also shown in the binding of MK and PTN to syndecan-1, suggesting the possibility of cooperation with the HS and/or CS chains in the binding of these growth factors and their delivery to the cell surface receptors.