title: Involvement of human natural killer-1 (HNK-1) sulfotransferase in the biosynthesis of the GlcUA(3-O-sulfate)-Gal-Gal-Xyl tetrasaccharide found in α-thrombomodulin from human urine.
abstract: Thrombomodulin (TM) is an integral membrane glycoprotein, which occurs as both a chondroitin sulfate (CS) proteoglycan (PG) form (β-TM) and a non-PG form without a CS chain (α-TM) and hence is a part-time PG. An α-TM preparation isolated from human urine contained the glycosaminoglycan linkage region tetrasaccharide GlcUAβ1-3Galβ1-3Galβ1-4xylose, and the nonreducing terminal GlcUA residue is 3-O-sulfated. Because the human natural killer-1 sulfotransferase (HNK-1ST) transfers a sulfate group from 3'-phosphoadenosine 5'-phosphosulfate to the C-3 position of the nonreducing terminal GlcUA residue in the HNK-1 antigen precursor trisaccharide, GlcUAβ1-3Galβ1-4GlcNAc, the sulfotransferase activity toward the linkage region was investigated. In fact, the activity of HNK-1ST toward the linkage region was much higher than that toward the glucuronylneolactotetraosylceramide, the precursor of the HNK-1 epitope. HNK-1ST may be responsible for regulating the sorting of α- and β-TM. Furthermore, HNK-1ST also transferred a sulfate group from 3'-phosphoadenosine 5'-phosphosulfate to the C-3 position of the nonreducing terminal GlcUA residue of a chondroitin chain. Intriguingly, the HNK-1 antibody recognized CS chains and the linkage region if they contained GlcUA(3-O-sulfate), suggesting that HNK-1ST not only synthesizes the HNK-1 epitope but may also be involved in the generation of part-time PGs.
authors.affiliation: Laboratory of Proteoglycan Signaling and Therapeutics, Frontier Research Center for Post-genomic Science and Technology, Graduate School of Life Science, Hokkaido University, West-11, North-21, Kita-ku, Sapporo, Hokkaido 001-0021, Japan.
authors.forename: Taishi
authors.initials: T
authors.lastname: Hashiguchi
authors.forename: Shuji
authors.initials: S
authors.lastname: Mizumoto
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nishimura
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Tamura
authors.forename: Shuhei
authors.initials: S
authors.lastname: Yamada
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Sugahara
mesh_terms: D000906:Antibodies / Q000276:immunology; D002809:Chondroitin Sulfates / Q000378:metabolism; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D002852:Chromatography, Ion Exchange; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D009844:Oligosaccharides / Q000096:biosynthesis*; D020033:Protein Isoforms / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013379:Substrate Specificity; D015238:Sulfotransferases / Q000276:immunology / Q000378:metabolism*; D018180:Thrombomodulin / Q000378:metabolism*; D014556:Urine / Q000737:chemistry*; D000097811:Carbohydrate Sulfotransferases
chemical_list: D000906:Antibodies; D002809:Chondroitin Sulfates; D006025:Glycosaminoglycans; D009844:Oligosaccharides; D020033:Protein Isoforms; D015238:Sulfotransferases; D018180:Thrombomodulin; C499549:CHST10 protein, human; D000097811:Carbohydrate Sulfotransferases