Galectin-1,-2, and-3 exhibit differential recognition of sialylated glycans and blood group antigens
Galectin-1,-2, and-3 exhibit differential recognition of sialylated glycans and blood group antigens
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DOI：
10.1074/jbc.m709545200
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发表时间：
2008-04-11
影响因子：
4.8
通讯作者：
Cummings, Richard D.
中科院分区：
文献类型：
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作者：
Stowell, Sean R.;Arthur, Connie M.;Cummings, Richard D.
尽管半乳糖凝集素家族的大多数成员与简单二糖乳糖 (Gal beta 1-4Glc) 的结合较弱，但人类半乳糖凝集素具有不同的功能。为了更详细地评估半乳糖凝集素-聚糖相互作用的特异性，我们使用剂量响应方法对包含数百个结构不同聚糖的聚糖微阵列探索了几种重要的半乳糖凝集素（Gal-1、Gal-2和Gal-3）的结合，并将这些结果与细胞上的结合决定簇进行了比较。所有三种半乳糖凝集素在聚糖结合特性上均表现出差异。在微阵列和细胞上，Gal-2 和 Gal-3 对含岩藻糖的 A 和 B 血型抗原的结合力高于 Gal-1。 Gal-2 与所有唾液酸化聚糖的结合显着降低，而 Gal-1 与 α 2-3-唾液酸化聚糖结合，但不与 α 2-6-唾液酸化聚糖结合，Gal-3 与一些以 α 2-3-或 α 2-6-唾液酸终止的聚糖结合。唾液酸化对 Gal-1、Gal-2 和 Gal-3 与细胞结合的影响也反映了细胞对 Gal-1、Gal-2 和 Gal-3 诱导的磷脂酰丝氨酸暴露的敏感性的差异。与 N-乙酰基乳糖胺 (LacNAc) 聚糖 (Gal beta 1-4GlcNAc) 相比，每种半乳糖凝集素对具有聚 N-乙酰基乳糖胺 (poly(LacNAc)) 序列 (Gal beta 1-4GlcNAc)(n) 的聚糖表现出更高的结合。然而，只有 Gal-3 与聚 (LacNAc) 内的内部 LacNAc 结合。这些结果表明，这些半乳糖凝集素中的每一种在与微阵列上的聚糖的结合方面在机制上有所不同，并且这些差异反映在细胞结合和信号转导所需的决定因素中。每种半乳糖凝集素的特异性聚糖识别强调了其生物活性差异的基础。
Human galectins have functionally divergent roles, although most of the members of the galectin family bind weakly to the simple disaccharide lactose (Gal beta 1-4Glc). To assess the specificity of galectin-glycan interactions in more detail, we explored the binding of several important galectins (Gal-1, Gal-2, and Gal-3) using a dose-response approach toward a glycan microarray containing hundreds of structurally diverse glycans, and we compared these results to binding determinants on cells. All three galectins exhibited differences in glycan binding characteristics. On both the microarray and on cells, Gal-2 and Gal-3 exhibited higher binding than Gal-1 to fucose-containing A and B blood group antigens. Gal-2 exhibited significantly reduced binding to all sialylated glycans, whereas Gal-1 bound alpha 2-3-but not alpha 2-6-sialylated glycans, and Gal-3 bound to some glycans terminating in either alpha 2-3- or alpha 2-6-sialic acid. The effects of sialylation on Gal-1, Gal-2, and Gal-3 binding to cells also reflected differences in cellular sensitivity to Gal-1-, Gal-2-, and Gal-3-induced phosphatidylserine exposure. Each galectin exhibited higher binding for glycans with poly-N-acetyllactosamine (poly(LacNAc)) sequences (Gal beta 1-4GlcNAc)(n) when compared with N-acetyllactosamine (LacNAc) glycans (Gal beta 1-4GlcNAc). However, only Gal-3 bound internal LacNAc within poly(LacNAc). These results demonstrate that each of these galectins mechanistically differ in their binding to glycans on the microarrays and that these differences are reflected in the determinants required for cell binding and signaling. The specific glycan recognition by each galectin underscores the basis for differences in their biological activities.