Binding of a large chondroitin sulfate/dermatan sulfate proteoglycan, versican, to L-selectin, P-selectin, and CD44

Binding of a large chondroitin sulfate/dermatan sulfate proteoglycan, versican, to L-selectin, P-selectin, and CD44
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DOI:
10.1074/jbc.m003387200
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发表时间:
2000-11-10
影响因子:
4.8
通讯作者:
Miyasaka, M
Miyasaka, M
中科院分区:
生物学2区
文献类型:
--
作者:
Kawashima, H;Hirose, M;Miyasaka, M

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这里:我们展示了一种来自肾腺癌细胞系ACHN的大分子硫酸软骨素蛋白多糖,它与L-选择素、P-选择素和CD_(44)结合。这种结合是通过Verscan的硫酸软骨素(CS)链与L-和P-选择素及CD44糖结合域的相互作用而实现的。万西康与L和P-选择素的结合可被CS B、CS E和硫酸乙酰肝素(HS)所抑制,但不被所测试的任何其他糖胺聚糖所抑制。另一方面,透明质酸、软骨素(CH)、CS A、CS B、CS C、CS D和CS E可抑制CD44的结合,而HS和硫酸角蛋白不能抑制CD44的结合。交叉阻断研究表明,L和P-选择素识别:文西嘉上的紧密或重叠的位点,而CD44识别不同的位点。我们还发现,可溶性L和P-选择素直接与固定化的CS B、CS E和HS结合,可溶性CD44直接与固定化的透明质酸、CH和所有CS链结合。与这些结果一致的是,结构分析表明Verscan至少被CS B和CB C修饰。因此,充分用适当的糖胺聚糖修饰的蛋白多糖应该能够:与L-选择素、P-选择素和/或CD44结合。
Here:we show that a large chondroitin sulfate proteoglycan, versican, derived from a renal adenocarcinoma cell line ACHN, binds L-selectin, P-selectin, and CD44. The binding was mediated by the interaction of the chondroitin:sulfate (CS) chain of versican with the carbohydrate-binding domain of L- and P-selectin and CD44. The binding of versican to L- and P-selectin was inhibited by CS B, CS E, and heparan sulfate (HS) but not by: any other glycosaminoglycans tested. On the other hand, the binding to CD44 was inhibited by hyaluronic acid, chondroitin (CH), CS A, CS B, CS C, CS D, and CS E but not by HS or keratan sulfate. A cross-blocking study indicated that L- and P-selectin recognize: close or overlapping sites on versican, whereas CD44 recognizes separate sites. We also show that soluble L- and P-selectin directly bind to immobilized CS B, CS E, and HS and that soluble CD44 directly binds to immobilized hyaluronic acid, CH, and all the CS chains examined. Consistent with these results, structural analysis showed that versican is modified with at least CS B and CB C. Thus, proteoglycans sufficiently modified with the appropriate glycosaminoglycans should be able: to bind L-selectin, P-selectin, and/or CD44.