The addition of bisecting <i>N</i>-acetylglucosamine residues to E-cadherin down-regulates the tyrosine phosphorylation of β-catenin

作     者：Kitada, T Miyoshi, E Noda, K Higashiyama, S Ihara, H Matsuura, N Hayashi, N Kawata, S Matsuzawa, Y Taniguchi, N 

作者机构：Osaka Univ Grad Sch Med Dept Biochem Suita Osaka 5650871 Japan Osaka Univ Grad Sch Med Dept Internal Med & Mol Sci Suita Osaka 5650871 Japan Osaka Univ Grad Sch Med Dept Mol Therapeut Suita Osaka 5650871 Japan Osaka Univ Fac Med Sch Allied Hlth Sci Dept Biochem Suita Osaka 5650871 Japan Osaka Univ Fac Med Sch Allied Hlth Sci Dept Pathol Suita Osaka 5650871 Japan 

出 版 物：《JOURNAL OF BIOLOGICAL CHEMISTRY》 (生物化学杂志)

年 卷 期：2001年第276卷第1期

页      面：475-480页

核心收录：

学科分类：0710[理学-生物学] 071010[理学-生物化学与分子生物学] 07[理学] 

主　　题：乙酰葡萄糖胺/化学 乙酰葡萄糖胺/遗传学 乙酰葡萄糖胺/代谢 印迹法 蛋白质 钙黏着糖蛋白类/化学 钙黏着糖蛋白类/遗传学 钙黏着糖蛋白类/代谢 碳水化合物序列 细胞大小/药物作用 细胞支架蛋白质类/代谢 酶激活 表皮生长因子/药理学 糖基化/药物作用 显微镜检查 荧光 分子序列数据 N-乙酰氨基葡糖转移酶类/遗传学 N-乙酰氨基葡糖转移酶类/代谢 磷酰化/药物作用 磷酸酪氨酸/代谢 RNA 信使/代谢 受体 表皮生长因子/代谢 重组融合蛋白质类/化学 重组融合蛋白质类/代谢 信号传导/药物作用 反式激活因子类 转染 肿瘤细胞 培养的 衣霉素/药理学 β连环素 src族激酶类/遗传学 动物 小鼠 

摘      要：The enzyme GnT-III (beta1,4-N-acetylglucosaminyltransferase III) catalyzes the addition of a bisecting N-acetylglucosamine (GlcNAc) residue on glycoproteins. Our previous study described that the transfection of GnT-lll into mouse melanoma cells results in the enhanced expression of E-cadherin, which in turn leads to, the suppression of lung metastasis. It has recently been proposed that the phosphorylation of a tyrosine residue of beta -catenin is associated with cell migration. The present study reports on the importance of bisecting GlcNAc residues by GnT-III on tyrosine phosphorylation of beta -catenin using three types of cancer cell lines. An addition of bisecting GlcNAc residues to E-cadherin leads to an alteration in cell morphology and the localization of beta -catenin after epidermal growth factor stimulation. These changes are the result of a down-regulation in the tyrosine phosphorylation of beta -catenin, In addition, tyrosine phosphorylation of beta -catenin by transfection of constitutively active c-src was suppressed in GnT-III transfectants as well as in the case of epidermal growth factor stimulation. Treatment with tunicamycin abolished any differences in beta -catenin phosphorylation for the mock vis a vis the GnT-III transfectants. Thus, the addition of a specific N-glycan structure, the bisecting GlcNAc to E-cadherin-beta -catenin complex, down-regulates the intracellular signaling pathway, suggesting its implication in cell motility and the suppression of cancer metastasis.