Sulfation of glucuronic acid in the linkage tetrasaccharide by HNK-1 sulfotransferase is an inhibitory signal for the expression of a chondroitin sulfate chain on thrombomodulin

被引:21
作者
Nakagawa, Naoki [1 ]
Izumikawa, Tomomi [2 ]
Kitagawa, Hiroshi [2 ]
Oka, Shogo [1 ]
机构
[1] Kyoto Univ, Grad Sch Med, Dept Biol Chem, Kyoto 6068507, Japan
[2] Kobe Pharmaceut Univ, Dept Biochem, Kobe, Hyogo 6588558, Japan
关键词
HNK-1 carbohydrate epitope; Thrombomodulin; HNK-1ST; GAG-protein linkage region; Anti-coagulant activity; CARBOHYDRATE EPITOPE HNK-1; MOLECULAR-CLONING; SOLUBLE THROMBOMODULIN; ALPHA-THROMBOMODULIN; BIOSYNTHESIS; GLUCURONOSYLTRANSFERASE; REGION; PROTEOGLYCANS; XYLOSE; GLYCOSAMINOGLYCANS;
D O I
10.1016/j.bbrc.2011.10.023
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
HNK-1 (human natural killer-1) carbohydrate epitope (HSO(3)-3GlcA beta 1-3Ga beta 1-4GlcNAc-) recognized by a HNK-1 monoclonal antibody is highly expressed in the nervous system and biosynthesized by a glucuronyltransferase (GIcAT-P or GlcAT-S), and sulfotransferase (HNK-1ST). A similar oligosaccharide (HSO(3)-3GlcA beta 1-3Gal beta 1-3Gal beta 1-4Xyl) also recognized by the HNK-1 antibody had been found in a glycosaminoglycan (GAG)-protein linkage region of alpha-thrombomodulin (TM) from human urine. However, which sulfotransferase is involved in sulfation of the terminal GlcA in the GAG-protein linkage region remains unclear. In this study, using CHO-K1 cells in which neither GIcAT-P nor GlcAT-S is endogenously expressed, we found that HNK-1ST has the ability to produce HNK-1 immunoreactivity on alpha-TM. We also demonstrated that HNK-1ST caused the suppression of chondroitin sulfate (CS) synthesis on TM and a reduction of its anti-coagulant activity. Moreover, using an in vitro enzyme assay system, the HNK-1-positive TM was found not to be utilized as a substrate for CS-polymerizing enzymes (chondroitin synthase (ChSy) and chondroitin polymerizing factor (ChPF)). These results suggest that HNK-1ST is involved in 3-O-sulfation of the terminal GlcA of the linkage tetrasaccharide which acts as an inhibitory signal for the initiation of CS biosynthesis on TM. (C) 2011 Elsevier Inc. All rights reserved.
引用
收藏
页码:109 / 113
页数:5
相关论文
共 30 条
[1]   Cloning and expression of a proteoglycan UDP-galactose:β-xylose β1,4-galactosyltransferase I -: A seventh member of the human β4-galactosyltransferase gene family [J].
Almeida, R ;
Levery, SB ;
Mandel, U ;
Kresse, H ;
Schwientek, T ;
Bennett, EP ;
Clausen, H .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (37) :26165-26171
[2]   Biosynthesis of the linkage region of glycosaminoglycans -: Cloning and activity of galactosyltransferase II, the sixth member of the β1,3-galactosyltransferase family (β3GalT6) [J].
Bai, XM ;
Zhou, DP ;
Brown, JR ;
Crawford, BE ;
Hennet, T ;
Esko, JD .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (51) :48189-48195
[3]  
ESMON CT, 1982, J BIOL CHEM, V257, P7944
[4]   STRUCTURE AND FUNCTION OF CELL-ASSOCIATED PROTEOGLYCANS [J].
FRANSSON, LA .
TRENDS IN BIOCHEMICAL SCIENCES, 1987, 12 (10) :406-411
[5]   Molecular cloning and expression of human UDP-D-xylose:proteoglycan core protein β-D-xylosyltransferase and its first isoform XT-II [J].
Götting, C ;
Kuhn, J ;
Zahn, R ;
Brinkmann, T ;
Kleesiek, K .
JOURNAL OF MOLECULAR BIOLOGY, 2000, 304 (04) :517-528
[6]   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 [J].
Hashiguchi, Taishi ;
Mizumoto, Shuji ;
Nishimura, Yuko ;
Tamura, Jun-ichi ;
Yamada, Shuhei ;
Sugahara, Kazuyuki .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2011, 286 (38) :33003-33011
[7]   Identification of chondroitin sulfate glucuronyltransferase as chondroitin synthase-3 involved in chondroitin polymerization - Chondroitin polymerization is achieved by multiple enzyme complexes consisting of chondroitin synthase family members [J].
Izumikawa, Tomomi ;
Koike, Toshiyasu ;
Shiozawa, Shoko ;
Sugahara, Kazuyuki ;
Tamura, Jun-Ichi ;
Kitagawa, Hiroshi .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (17) :11396-11406
[8]   Regulation of chondroitin sulfate biosynthesis by specific sulfation: Acceptor specificity of serum beta-GalNAc transferase revealed by structurally defined oligosaccharides [J].
Kitagawa, H ;
Tsutsumi, K ;
Ujikawa, M ;
Goto, F ;
Tamura, J ;
Neumann, KW ;
Ogawa, T ;
Sugahara, K .
GLYCOBIOLOGY, 1997, 7 (04) :531-537
[9]   Molecular cloning and expression of glucuronyltransferase I involved in the biosynthesis of the glycosaminoglycan-protein linkage region of proteoglycans [J].
Kitagawa, H ;
Tone, Y ;
Tamura, J ;
Neumann, KW ;
Ogawa, T ;
Oka, S ;
Kawasaki, T ;
Sugahara, K .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (12) :6615-6618
[10]   Molecular cloning of a chondroitin polymerizing factor that cooperates with chondroitin synthase for chondroitin polymerization [J].
Kitagawa, H ;
Izumikawa, T ;
Uyama, T ;
Sugahara, K .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (26) :23666-23671