Regulation of cytokine receptors by Golgi N-glycan processing and endocytosis
Regulation of cytokine receptors by Golgi N-glycan processing and endocytosis
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DOI：
10.1126/science.1102109
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发表时间：
2004-10-01
期刊：
影响因子：
56.9
通讯作者：
Dennis, JW
中科院分区：
文献类型：
--
作者：
Partridge, EA;Le Roy, C;Dennis, JW
高尔基体酶β 1，6 N-乙酰葡糖胺转移酶V（Mgat 5）在癌中上调，并促进N-聚糖被聚N-乙酰乳糖胺（半乳糖凝集素-3（Gal-3）的优选配体）取代。在这里，我们报告了Mgat 5的表达使小鼠细胞对多种细胞因子敏感。Gal-3交联细胞表面表皮生长因子和转化生长因子β受体上的Mgat 5修饰的N-聚糖，并通过组成性内吞作用延迟其去除。乳腺癌中的Mgat 5表达是细胞因子信号传导的限速因子，因此也是上皮-间质转化、细胞运动和肿瘤转移的限速因子。Mgat 5还促进了体内白细胞介导的白细胞信号传导、吞噬作用和外渗。因此，N-聚糖加工的条件调节驱动细胞因子受体的同步修饰，这平衡了它们的表面保留与通过内吞作用的损失。
The Golgi enzyme beta1,6 N-acetylglucosaminyltransferase V (Mgat5) is upregulated in carcinomas and promotes the substitution of N-glycan with poly N-acetyllactosamine, the preferred ligand for galectin-3 (Gal-3). Here, we report that expression of Mgat5 sensitized mouse cells to multiple cytokines. Gal-3 cross-linked Mgat5-modified N-glycans on epidermal growth factor and transforming growth factor-beta receptors at the cell surface and delayed their removal by constitutive endocytosis. Mgat5 expression in mammary carcinoma was rate limiting for cytokine signaling and consequently for epithelial-mesenchymal transition, cell motility, and tumor metastasis. Mgat5 also promoted cytokine-mediated leukocyte signaling, phagocytosis, and extravasation in vivo. Thus, conditional regulation of N-glycan processing drives synchronous modification of cytokine receptors, which balances their surface retention against loss via endocytosis.