Laferté S, Dennis J W
Division of Cancer and Cell Biology, Mount Sinai Hospital Research Institute, Toronto, Ontario, Canada.
Cancer Res. 1988 Sep 1;48(17):4743-8.
Two highly glycosylated membrane sialoglycoproteins designated P2A and P2B were isolated from the lymphoreticular tumor cell line called MDAY-D2 and shown to be structurally similar to the lymphocyte glycoprotein called leukosialin and to lysosome-associated membrane glycoprotein termed LAMP-1, respectively. The loss of sialic acid and polylactosamine sequences in glycosylation mutants of MDAY-D2 has been correlated previously with enhanced cell adhesion on extracellular matrix proteins. Since these two glycoproteins bear the majority of the sialylated oligosaccharides found in membrane fractions of MDAY-D2, they were tested for binding activity on extracellular matrix proteins. Both isolated glycoproteins bound to immobilized collagen type I with affinities that were dependent on their glycosylation. Enzymatic removal of sialic acid, polylactosamine, or complete asparagine-linked chains from purified P2B enhanced its binding to collagen, laminin, and fibronectin. In contrast, P2A bound specifically to collagen type I and the interaction required the presence of sialic acid residues which were sensitive to neuraminidase digestion but not to endoglycosidase F. The results suggest that oncodevelopmental regulation of oligosaccharide expression on P2A and P2B glycoproteins may modulate their binding to extracellular matrix glycoproteins.
从名为MDAY-D2的淋巴网状肿瘤细胞系中分离出两种高度糖基化的膜唾液酸糖蛋白，分别命名为P2A和P2B。结果表明，它们在结构上分别与淋巴细胞糖蛋白白细胞唾液酸蛋白和溶酶体相关膜糖蛋白LAMP-1相似。先前已发现，MDAY-D2糖基化突变体中唾液酸和聚乳糖胺序列的缺失与细胞在细胞外基质蛋白上的黏附增强有关。由于这两种糖蛋白携带了MDAY-D2膜组分中发现的大部分唾液酸化寡糖，因此对它们在细胞外基质蛋白上的结合活性进行了测试。两种分离出的糖蛋白都以依赖于其糖基化的亲和力与固定化的I型胶原结合。从纯化的P2B中酶促去除唾液酸、聚乳糖胺或完整的天冬酰胺连接链，可增强其与胶原、层粘连蛋白和纤连蛋白的结合。相比之下，P2A特异性结合I型胶原，且这种相互作用需要存在对神经氨酸酶消化敏感但对内切糖苷酶F不敏感的唾液酸残基。结果表明，P2A和P2B糖蛋白上寡糖表达的肿瘤发生发育调控可能会调节它们与细胞外基质糖蛋白的结合。
