N-GLYCOSYLATION OF THE HUMAN GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR-RECEPTOR ALPHA-SUBUNIT IS ESSENTIAL FOR LIGAND-BINDING AND SIGNAL-TRANSDUCTION
N-GLYCOSYLATION OF THE HUMAN GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR-RECEPTOR ALPHA-SUBUNIT IS ESSENTIAL FOR LIGAND-BINDING AND SIGNAL-TRANSDUCTION
复制标题
DOI：
10.1074/jbc.270.41.24580
复制
发表时间：
1995-10-13
影响因子：
4.8
通讯作者：
GOLDE, DW
中科院分区：
文献类型：
--
作者：
DING, DXH;VERA, JC;GOLDE, DW
人粒细胞-巨噬细胞集落刺激因子（GM-CSF）受体α亚基是一种糖蛋白，在其胞外区含有11个潜在的N-糖基化位点。我们研究了N-糖基化对α亚基膜定位和功能的影响。N-糖基化抑制剂衣霉素（Tunicamycin）能显著抑制GM-CSF结合、GM-CSF诱导的脱氧葡萄糖摄取、和蛋白酪氨酸磷酸化，但不影响α亚基的细胞表面表达，如抗α亚基单克隆抗体所检测的。在表达α亚基并用衣霉素处理的COS细胞中，N-非糖基化α亚基表达并转运至细胞表面，但不能结合GM-CSF。在COS细胞表达α和β亚基的高亲和力结合也被衣霉素处理阻断。这些研究表明，N-连接的寡糖对于人GM-CSF受体的α亚单位配体结合和信号传导是必需的。
The alpha subunit of the receptor for human granulocyte-macrophage colony-stimulating factor (GM-CSF) is a glycoprotein containing 11 potential N-glycosylation sites in the extracellular domain, We examined the role of N-glycosylation on alpha subunit membrane localization and function, Tunicamycin, an N-glycosylation inhibitor, markedly inhibited GM-CSF binding, GM-CSF-induced deoxyglucose uptake, and protein tyrosine phosphorylation in HL-60(eos) cells but did not affect cell surface expression of the alpha subunit as detected by an anti-alpha subunit monoclonal antibody, In COS cells expressing the alpha subunit and treated with tunicamycin, N-unglycosylated alpha subunit was expressed and transported to the cell surface but was not capable of binding GM-CSF. High affinity binding in COS cells expressing both alpha and beta subunits was also blocked by tunicamycin treatment. These studies indicate that N-linked oligosaccharides are essential for alpha subunit ligand binding and signaling by the human GM-CSF receptor.