Sulfation pattern in glycosaminoglycan: does it have a code?
Heparan sulfate chains (HS) are initially synthesized on core proteins as linear polysaccharides composed of glucuronic acid--N-acetylglucosamine repeating units and subjected to marked structural modification by sulfation (N-, 2-O-, 6-O-, 3-O-sulfotransferases) and epimerization (C5-epimerase) at the Golgi lumen and further by desulfation (6-O- endosulfatase) at the cell surface, after which divergent fine structures are generated. The expression patterns and specificity of the modifying enzymes are, at least partly, responsible for the elaboration of these fine structures of heparan sulfate. HS interacts with many proteins including growth factors (GF) and morphogens through specific fine structures. Recent biochemical and genetic studies have presented evidence that HS plays important roles in cell behavior and organogenesis. In knock-down experiments of heparan sulfate 6-O-sulfotransferase, 6-O-sulfated units in HS have been shown to act as a stimulator or suppressor according to individual GF/morphogen signaling systems.
Institute for Molecular Science of Medicine, Aichi Medical University, Nagakute, Aichi 480-1195, Japan.
Hiroko
H
Habuchi
Osami
O
Habuchi
Koji
K
Kimata
D000818:Animals; D002238:Carbohydrate Epimerases / Q000737:chemistry; D002642:Chick Embryo; D020723:Glucuronic Acid / Q000737:chemistry; D006025:Glycosaminoglycans / Q000737:chemistry*; D006056:Golgi Apparatus / Q000378:metabolism*; D006133:Growth Substances / Q000378:metabolism; D019812:Heparan Sulfate Proteoglycans / Q000737:chemistry; D006497:Heparan Sulfate / Q000737:chemistry; D006801:Humans; D051379:Mice; D011134:Polysaccharides / Q000737:chemistry; D020033:Protein Isoforms; D015398:Signal Transduction; D013379:Substrate Specificity; D015238:Sulfotransferases / Q000378:metabolism; D015027:Zebrafish
D002238:Carbohydrate Epimerases; D020723:Glucuronic Acid; D006025:Glycosaminoglycans; D006133:Growth Substances; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D011134:Polysaccharides; D020033:Protein Isoforms; D015238:Sulfotransferases; C086519:mannuronan c-5-epimerase