High Endothelial Cell N-Acetylglucosamine 6-O-Sulfotransferase

Abstract

High endothelial cell (HEC)-specific N-acetylglucosamine 6-sulfotransferase (HEC- GlcNAc6ST) (Bistrup et al. 1999), or L-selectin ligand sulfotransferase (LSST) (Hiraoka et al. 1999), is a transmembrane protein of 386 amino acids with a short, N-terminal cytoplasmic tail and a large luminal C-terminal catalytic domain. This enzyme belongs to a recently identified family of carbohydrate sulfotransferases that modify the 6-hydroxyl of Gal, GalNAc, or GlcNAc residues (GST family) (Rosen et al. 1999; Hemmerich and Rosen 2000). In addition to HEC-GlcNAc6ST, there are two other GlcNAc-6 sulfotransferases in this family: N-acetylglucosamine 6- sulfotransferase [GlcNAc6ST (Uchimura et al. 1998a, b) or CHST2 (Li and Tedder 1999)] and intestinal N-acetylglucosamine 6-sulfotransferase (I-GlcNAc6ST) (Lee et al. 1999). Within their sulfotransferase domains, these three enzymes are more than 27% identical at the amino acid level and more than 56% similar. HEC-GlcNAc6ST is expressed in a limited number of tissues and is highly enriched in HECs (Bistrup et al. 1999; Hiraoka et al. 1999). In contrast, GlcNAc6ST is expressed ubiquitously (Uchimura et al. 1998b), and I-GlcNAc6ST is expressed almost exclusively in intestinal tissues (Lee et al. 1999). A recently identified chondroitin 6-O-sulfotransferase, designated C6ST-2 (Kitagawa et al. 2000), exhibits GalNAc 6-sulfotransferase activity toward chondroitin (Kitagawa et al. 2000). The other members of this novel family, keratan sulfate 6-sulfotransferase [KSGal6ST (Fukuta et al. 1997); CHST1 (Li and Tedder 1999)] and chondroitin 6-sulfotransferase (C6ST) (Fukuta et al. 1998), have galactose 6-sulfotransferase activity; in addition, C6ST catalyzes sulfation at C-6 of GalNAc in chondroitin sulfate (Fukuta et al. 1997).