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N-连接寡糖加工抑制剂对黑色素瘤整合素细胞表面表达的影响

Effect of inhibitors of N-linked oligosaccharide processing on the cell surface expression of a melanoma integrin.

作者信息

Spiro R C, Laufer D M, Perry S K, Harper J R

机构信息

Department of Immunology, Research Institute of Scripps Clinic, La Jolla, California 92037.

出版信息

J Cell Biochem. 1989 Sep;41(1):37-45. doi: 10.1002/jcb.240410105.

DOI:10.1002/jcb.240410105
PMID:2480355
Abstract

The role of trimming and processing of N-linked oligosaccharides on the cell surface expression of the melanoma vitronectin receptor, a member of the integrin family of cell adhesion receptors, was examined by using specific glucosidase and mannosidase inhibitors. Inhibition of glucosidases I and II by castanospermine or N-methyldeoxynojirimycin delayed the vitronectin receptor alpha/beta chain heterodimer assembly and alpha chain cleavage and resulted in a decrease in the level of expression cell surface receptor. Conversely, the vitronectin receptor synthesized in the presence of the mannosidase I and II inhibitors, 1-deoxymannojirimycin and swainsonine, was transported normally to the cell surface with its alpha chain N-linked oligosaccharides in an endoglycosidase H-sensitive form. In the presence of swainsonine, time course studies of the cell surface replacement of control, endoglycosidase H-resistant receptor with an endoglycosidase H-sensitive form demonstrated a vitronectin receptor half-life of approximately 15-16 h. These studies provide evidence that the rates of assembly, proteolytic cleavage, and cell surface expression of the melanoma vitronectin receptor are dependent on the initial trimming of glucosyl residues from the alpha chain N-linked oligosaccharides.

摘要

通过使用特定的葡糖苷酶和甘露糖苷酶抑制剂,研究了N-连接寡糖的修剪和加工对黑素瘤玻连蛋白受体(一种细胞粘附受体整合素家族的成员)细胞表面表达的作用。栗精胺或N-甲基脱氧野尻霉素对葡糖苷酶I和II的抑制作用延迟了玻连蛋白受体α/β链异二聚体的组装和α链的切割,并导致细胞表面受体表达水平降低。相反,在甘露糖苷酶I和II抑制剂1-脱氧甘露野尻霉素和苦马豆素存在的情况下合成的玻连蛋白受体,其α链N-连接寡糖以对内切糖苷酶H敏感的形式正常转运到细胞表面。在苦马豆素存在的情况下,对用对内切糖苷酶H敏感形式的对照、对内切糖苷酶H抗性受体进行细胞表面置换的时间进程研究表明,玻连蛋白受体的半衰期约为15 - 16小时。这些研究提供了证据,表明黑素瘤玻连蛋白受体的组装、蛋白水解切割和细胞表面表达速率取决于α链N-连接寡糖中葡糖基残基的初始修剪。

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