Golgi localization of carbohydrate sulfotransferases is a determinant of L-selectin ligand biosynthesis
Golgi localization of carbohydrate sulfotransferases is a determinant of L-selectin ligand biosynthesis
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DOI：
10.1074/jbc.m304928200
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发表时间：
2003-10-10
影响因子：
4.8
通讯作者：
Bertozzi, CR
中科院分区：
文献类型：
--
作者：
de Graffenried, CL;Bertozzi, CR
硫转移酶GlcNAc6ST-2对内皮糖蛋白的硫酸化是一种促进白细胞粘附分子l -选择素结合的调节修饰。GlcNAc6ST-2是一个相关酶家族的成员，在体外作用于相似的碳水化合物底物，但在体内作用于不同的糖蛋白。研究表明，GlcNAc6ST-1、-2和-3具有明显的高尔基分布，其中GlcNAc6ST-1局限于反式高尔基网络，GlcNAc6ST-3局限于早期分泌通路，而GlcNAc6ST-2分布于整个高尔基体。它们的定位与n -连接或o -连接糖蛋白的优先活性相关。由GlcNAc6ST-1的定位域与GlcNAc6ST-2的催化域融合的嵌合体被限制在反式高尔基网络中，并采用GlcNAc6ST-1的底物偏好。我们提出了一个高尔基酶定位和竞争协调l -选择素配体的生物合成的模型。
Sulfation of endothelial glycoproteins by the sulfotransferase GlcNAc6ST-2 is a regulatory modification that promotes binding of the leukocyte adhesion molecule L-selectin. GlcNAc6ST-2 is a member of a family of related enzymes that act on similar carbohydrate substrates in vitro but discrete glycoproteins in vivo. We demonstrate that GlcNAc6ST-1, -2, and -3 have distinct Golgi distributions, with GlcNAc6ST-1 confined to the trans-Golgi network, GlcNAc6ST-3 confined to the early secretory pathway, and GlcNAc6ST-2 distributed throughout the Golgi. Their localization was correlated with preferred activity on either N-linked or O-linked glycoproteins. A chimera comprising the localization domain of GlcNAc6ST-1 fused to the catalytic domain of GlcNAc6ST-2 was confined to the trans-Golgi network and adopted the substrate preference of GlcNAc6ST-1. We propose a model in which Golgi enzyme localization and competition orchestrate the biosynthesis of L-selectin ligands.