Baeuerle P A, Huttner W B
EMBO J. 1984 Oct;3(10):2209-15. doi: 10.1002/j.1460-2075.1984.tb02118.x.
Immunoglobulin G2a (IgG2a) secreted by the hybridoma line M 31 was found to contain covalently linked sulphate. The sulphate was bound to the heavy chain which existed in several isoelectric variants. All variants were sulphated, the more acidic ones being more highly sulphated. Within the heavy chain the sulphate was not linked to tyrosine, threonine or serine residues, but appeared to be bound to N-linked oligosaccharides located in the Fab-portion. In contrast, the N-linked oligosaccharides in the Fc-portion were unsulphated. Surprisingly, the unglycosylated IgG secreted in the presence of tunicamycin, an inhibitor of N-glycosylation, was not unsulphated, but contained four times as much sulphate on the heavy chain as control IgG. All isoelectric variants of the non-glycosylated heavy chain contained sulphate. This sulphate was localized in the Fc-portion and was largely bound to tyrosine residues. These results show that, upon inhibition of N-glycosylation, the IgG is not simply secreted in non-glycosylated form, but has undergone a different post-translational modification, tyrosine sulphation. We discuss the possibility that tyrosine sulphate residues functionally compensate for the absence of N-linked (sulphated) oligosaccharides in IgG. One common function for these two protein modifications could be to serve as signals for the secretion of IgG.
杂交瘤细胞系M 31分泌的免疫球蛋白G2a（IgG2a）被发现含有共价连接的硫酸盐。硫酸盐与存在几种等电变体的重链结合。所有变体都被硫酸化，酸性越强的变体硫酸化程度越高。在重链中，硫酸盐不与酪氨酸、苏氨酸或丝氨酸残基相连，而是似乎与位于Fab部分的N-连接寡糖结合。相比之下，Fc部分的N-连接寡糖未被硫酸化。令人惊讶的是，在N-糖基化抑制剂衣霉素存在下分泌的未糖基化IgG并未未被硫酸化，而是重链上的硫酸盐含量是对照IgG的四倍。未糖基化重链的所有等电变体都含有硫酸盐。这种硫酸盐定位于Fc部分，并且大部分与酪氨酸残基结合。这些结果表明，在抑制N-糖基化后，IgG并非简单地以未糖基化形式分泌，而是经历了不同的翻译后修饰，即酪氨酸硫酸化。我们讨论了酪氨酸硫酸化残基在功能上补偿IgG中N-连接（硫酸化）寡糖缺失的可能性。这两种蛋白质修饰的一个共同功能可能是作为IgG分泌的信号。
