Epidermal growth factor receptor glycosylation is required for ganglioside GM3 binding and GM3-mediated suppression [correction of suppresion] of activation.
Epidermal growth factor receptor glycosylation is required for ganglioside GM3 binding and GM3-mediated suppression [correction of suppresion] of activation.
复制标题
表皮生长因子受体糖基化是神经节苷脂 GM3 结合和 GM3 介导的激活抑制（抑制的校正）所必需的。
DOI：
10.1093/glycob/11.7.515
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发表时间：
2001
期刊：
影响因子：
4.3
通讯作者：
Paller,AS
中科院分区：
文献类型：
--
作者：
Wang,XQ;Sun,P;O'Gorman,M;Tai,T;Paller,AS
神经节苷脂能够与表皮生长因子受体结合并抑制其活化，但这种抑制的机制尚不清楚。为了解决受体碳水化合物在促进与神经节苷脂相互作用中的作用，我们检测了GM3结合去糖基化受体并抑制其自身磷酸化的能力。流式细胞术研究表明，受体的去糖基化不影响其被转运到细胞膜的能力。与天然（完全糖基化）受体相反，GM3不与去糖基化受体共免疫沉淀。使用一种新的比色珠结合试验，GM3显示出良好的结合免疫沉淀的天然受体，但不是在所有的去糖基化的受体。最后，向具有去糖基化表皮生长因子受体的细胞中添加GM3并没有导致受体自磷酸化的显著进一步抑制，尽管200 µM GM3使天然表皮生长因子受体的磷酸化降低了10倍。这些研究表明，神经节苷脂影响表皮生长因子受体的活性，通过直接相互作用，需要受体糖基化，并有助于我们了解神经节苷脂在细胞膜功能中的作用。
Gangliosides are able to bind to the epidermal growth factor receptor and inhibit its activation, but the mechanism of this inhibition is unknown. To address the role of receptor carbohydrates in facilitating interaction with gangliosides, we examined the ability of GM3 to bind the deglycosylated receptor and inhibit its autophosphorylation. Flow cytometry studies demonstrated that deglycosylation of the receptor did not affect its ability to be transported to the cell membrane. In contrast with the native (fully glycosylated) receptor, GM3 did not coimmunoprecipitate with the deglycosylated receptor. Using a novel colorimetric bead binding assay, GM3 was shown to bind well to the immunoprecipitated native receptor but not at all to the deglycosylated receptor. Finally, the addition of GM3 to cells with deglycosylated epidermal growth factor receptors did not result in significant further inhibition of autophosphorylation of the receptor, despite a 10-fold decrease in phosphorylation of the native epidermal growth factor receptor by 200 µM GM3. These studies suggest that ganglioside affects epidermal growth factor receptor activity through a direct interaction that requires receptor glycosylation,and contribute to our understanding of the role of gangliosides in cell membrane function.