Regulation of Epidermal Growth Factor Receptor Through Interaction of Ganglioside GM3 with GlcNAc of N-Linked Glycan of the Receptor: Demonstration in ldlD Cells
Regulation of Epidermal Growth Factor Receptor Through Interaction of Ganglioside GM3 with GlcNAc of N-Linked Glycan of the Receptor: Demonstration in ldlD Cells
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DOI：
10.1007/s11064-010-0379-9
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发表时间：
2011-09-01
影响因子：
4.4
通讯作者：
Hakomori, Sen-itiroh
中科院分区：
文献类型：
--
作者：
Guan, Feng;Handa, Kazuko;Hakomori, Sen-itiroh
我们研究了GM 3与表皮生长因子受体（EGFR）N-连接聚糖的N-乙酰葡萄糖胺（GlcNAc）末端的相互作用，作为GM 3对EGFR活化的抑制作用的潜在机制，使用转染EGFR基因的ldlD细胞。这些细胞在UDP-Gal/UDP-GalNAc 4-差向异构酶中有缺陷，不能合成含半乳糖（Gal）的聚糖，除非在培养物中提供Gal（+Gal）。关键观察结果：（1）GlcNAc末端的表达在-Gal细胞中高，并且在+Gal细胞中强烈降低。(2)外源添加的GM 3对+Gal与-Gal细胞中EGFR活化的抑制作用的比较研究表明，EGFR上更高水平的GlcNAc末端与GM 3的更大抑制作用相关。(3)GM 3-，而不是GM 1-，包被的珠粒结合EGFR的-Gal细胞的裂解物，其具有高度暴露的GlcNAc末端。这种结合在EDTA存在下被抑制，类似于其他碳水化合物-碳水化合物相互作用。
We investigated interaction of GM3 with N-acetylglucosamine (GlcNAc) termini of N-linked glycans of epidermal growth factor receptor (EGFR), as the underlying mechanism for inhibitory effect of GM3 on EGFR activation, using ldlD cells transfected with EGFR gene. These cells, defective in UDP-Gal/UDP-GalNAc 4-epimerase, are incapable of synthesizing galactose (Gal)-containing glycans, unless Gal is provided in culture (+Gal). Key observations: (1) Expression of GlcNAc termini was high in -Gal cells, and strongly reduced in +Gal cells. (2) Comparative study of inhibitory effect of exogenously-added GM3 on EGFR activation in +Gal versus -Gal cells indicated that higher level of GlcNAc termini on EGFR is correlated with greater inhibitory effect of GM3. (3) GM3-, but not GM1-, coated beads bound to EGFR in lysate of -Gal cells, which have highly exposed GlcNAc termini. Such binding was inhibited in the presence of EDTA, similarly to other carbohydrate-carbohydrate interactions.