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Galactosaminoglycan Uronyl 2-Sulfotransferase

  • Nicholas W. Shworak
  • Robert D. Rosenberg

Abstract

The glycosaminoglycan (GAG) side chains of proteoglycans exhibit structural diversity that allows participation in numerous biologic functions. Structural diversity is in part dependent on the abundance and placement of 2-sulfated uronyl residues. These components are highly abundant in the GAGs heparan sulfate and heparin but are infrequent in the galactosaminoglycans. For example, dermatan sulfate is predominantly composed of IdoA→GalNAc-4S and to a lesser extent GlcA→GalNAc-4. However, the 2-sulfated unit IdoA-2S→GalNAc-4S can also occur in minor amounts (5%–10% of total disaccharides) (Maimone and Tollefsen 1991). Similarly, chon- droitin sulfate principally contains GlcA→GalNAc-4S, GlcA→GalNAc-6S, or both; low amounts of GlcA-2S→GalNAc-6S may also be present (Cheng et al. 1994). Such paucity makes 2-sulfated uronyl residues ideal candidates for regulating selected biologic activities of dermatan sulfate/chondroitin sulfate. This chapter describes the recent isolation and characterization of the enzyme galactosaminoglycan uronyl 2- sulfotransferase, which is capable of adding this rare substituent to dermatan sulfate and chondroitin sulfate (Kobayashi et al. 1999).

Keywords

Heparan Sulfate Chondroitin Sulfate Dermatan Sulfate Chondroitin Sulfate Proteoglycan Donor Plasmid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Avnur Z, Geiger B (1984) Immunocytochemical localization of native chondroitin-sulfate in tissues and cultured cells using specific monoclonal antibody. Cell 38:811–822PubMedCrossRefGoogle Scholar
  2. Brooks B, Briggs DM, Eastmond NC, Fernig DG, Coleman JW (2000) Presentation of IFN-gamma to nitric oxide-producing cells: a novel function for mast cells. J Immunol 164:573–579PubMedGoogle Scholar
  3. Cheng F, Heinegard D, Malmstrom A, Schmidtchen A, Yoshida K, Fransson LA (1994) Patterns of uronyl epimerization and 4-/6-O-sulphation in chondroitin/dermatan sulphate from decorin and biglycan of various bovine tissues. Glycobiology 4:685–696PubMedCrossRefGoogle Scholar
  4. Davidson S, Gilead L, Amira M, Ginsburg H, Razin E (1990) Synthesis of chondroitin sulfate D and heparin proteoglycans in murine lymph node-derived mast cells: the dependence on fibroblasts. J Biol Chem 265:12324–12330PubMedGoogle Scholar
  5. Faissner A, Clement A, Lochter A, Streit A, Mandl C, Schachner M (1994) Isolation of a neural chondroitin sulfate proteoglycan with neurite outgrowth promoting properties. J Cell Biol 126:783–799PubMedCrossRefGoogle Scholar
  6. Kobayashi M, Sugumaran G, Liu J, Shworak NW, Silbert JE, Rosenberg RD (1999) Molecular cloning and characterization of a human uronyl 2-sulfotransferase that sulfates iduronyl and glucuronyl residues in dermatan/chondroitin sulfate. J Biol Chem 274:10474–10480PubMedCrossRefGoogle Scholar
  7. Lyon M, Deakin JA, Rahmoune H, Fernig DG, Nakamura T, Gallagher JT (1998) Hepatocyte growth factor/scatter factor binds with high affinity to dermatan sulfate. J Biol Chem 273:271–278PubMedCrossRefGoogle Scholar
  8. Maimone MM, Tollefsen DM (1990) Structure of a dermatan sulfate hexasaccharide that binds to heparin cofactor II with high affinity. J Biol Chem 265:18263–18271PubMedGoogle Scholar
  9. Maimone MM, Tollefsen DM (1991) Structure of a dermatan sulfate hexasaccharide that binds to heparin cofactor II with high affinity. J Biol Chem 266:14830PubMedGoogle Scholar
  10. Mark MP, Baker JR, Kimata K, Ruch JV (1990) Regulated changes in chondroitin sulfation during embryogenesis: an immunohistochemical approach. Int J Dev Biol 34:191–204PubMedGoogle Scholar
  11. Nadanaka S, Clement A, Masayama K, Faissner A, Sugahara K (1998) Characteristic hexasaccharide sequences in octasaccharides derived from shark cartilage chondroitin sulfate D with a neurite outgrowth promoting activity. J Biol Chem 273:3296–3307PubMedCrossRefGoogle Scholar
  12. Penc SF, Pomahac B, Eriksson E, Detmar M, Gallo RL (1999) Dermatan sulfate activates nuclear factor-Kb and induces endothelial and circulating intercellular adhesion molecule-1. J Clin Invest 103:1329–1335PubMedCrossRefGoogle Scholar
  13. Penc SF, Pomahac B, Winkler T, Dorschner RA, Eriksson E, Herndon M, Gallo RL (1998) Dermatan sulfate released after injury is a potent promoter of fibroblast growth factor-2 function. J Biol Chem 273:28116–28121PubMedCrossRefGoogle Scholar
  14. Shukla D, Liu J, Blaiklock P, Shworak NW, Bai X, Esko JD, Cohen GH, Eisenberg RJ, Rosenberg RD, Spear PG (1999) A novel role for 3-O-sulfated heparan sulfate in herpes simplex virus 1 entry. Cell 99:13–22PubMedCrossRefGoogle Scholar
  15. Shworak NW, Fritze LMS, Liu J, Butler LD, Rosenberg RD (1996) Cell-free synthesis of anticoagulant heparan sulfate reveals a limiting activity which modifies a nonlimiting precursor pool. J Biol Chem 271:27063–27071PubMedCrossRefGoogle Scholar
  16. Shworak NW, Liu J, Petros LM, Zhang L, Kobayashi M, Copeland NG, Jenkins NA, Rosenberg RD (1999) Multiple isoforms of heparan sulfate D-glucosaminyl 3-O-sulfotransferase: isolation, characterization, and expression of human cDNAs and identification of distinct genomic loci. J Biol Chem 274:5170–5184PubMedCrossRefGoogle Scholar
  17. Spillmann D, Witt D, Lindahl U (1998) Defining the interleukin-8-binding domain of heparan sulfate. J Biol Chem 273:15487–15493PubMedCrossRefGoogle Scholar
  18. Turnbull JE, Fernig DG, Ke Y, Wilkinson MC, Gallagher JT (1992) Identification of the basic fibroblast growth factor binding sequence in fibroblast heparan sulfate. J Biol Chem 267:10337–10341PubMedGoogle Scholar
  19. Yamagata M, Kimata K, Oike Y, Tani K, Maeda N, Yoshida K, Shimomura Y, Yoneda M, Suzuki S (1987) A monoclonal antibody that specifically recognizes a glucuronic acid 2-sulfate-containing determinant in intact chondroitin sulfate chain. J Biol Chem 262:4146–4152PubMedGoogle Scholar

Copyright information

© Springer Japan 2002

Authors and Affiliations

  • Nicholas W. Shworak
    • 1
    • 2
    • 3
  • Robert D. Rosenberg
    • 1
    • 2
  1. 1.Department of Medicine, Harvard Medical SchoolAngiogenesis Research Center, SL-418, BethIsrael Deaconess Medical CenterBostonUSA
  2. 2.Department of BiologyMassachusetts Institute of TechnologyCambridgeUSA
  3. 3.Department of Medicine, Dartmouth Medical SchoolAngiogenesis Research Center, HB7504 Dartmouth Mitchcock Medical CenterLebanonUSA

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