title: Uronyl 2-O sulfotransferase potentiates Fgf2-induced  cell migration.
abstract: Fibroblast growth factor 2 (Fgf2) is involved in several biological functions. Fgf2 requires glycosaminoglycans, like chondroitin and dermatan sulfates (hereafter denoted CS/DS) as co-receptors. CS/DS are linear polysaccharides composed of repeating disaccharide units [-4GlcUAb1-3-GalNAc-b1-] and [-4IdoUAa1-3-GalNAc-b1-],which can be sulfated. Uronyl 2-O-sulfotransferase (Ust)introduces sulfation at the C2 of IdoUA and GlcUA resulting inover-sulfated units. Here, we investigated the role of Ust-mediated CS/DS 2-O sulfation in Fgf2-induced cell migration. We found that CHO-K1 cells overexpressing Ust contain significantly more CS/DS2-O sulfated units, whereas Ust knockdown abolished CS/DS 2-O sulfation. These structural differences in CS/DS resulted in altered Fgf2 binding and increased phosphorylation of ERK1/2 (also known as MAPK3 and MAPK1, respectively). As a functional consequence of CS/DS 2-O sulfation and altered Fgf2 binding, cell migration and paxillin activation were increased. Inhibition of sulfation, knockdown of Ust and inhibition of FgfR resulted in reduced migration. Similarly, in 3T3 cells Fgf2 treatment increased migration, which was abolished by Ust knockdown. The proteoglycan controlling the CHO migration was syndecan 1. Knockdown of Sdc1 in CHO-K1 cells overexpressing Ust abolished cell migration.We conclude that the presence of distinctly sulfated CS/DS can tune the Fgf2 effect on cell migration.
authors.forename: Katerina
authors.initials: K
authors.lastname: Nikolovska
authors.forename: Dorothe
authors.initials: D
authors.lastname: Spillmann
authors.forename: Daniela G
authors.initials: DG
authors.lastname: Seidler
mesh_terms: D016475:3T3 Cells; D000818:Animals; D016466:CHO Cells; D002460:Cell Line; D002465:Cell Movement; D002809:Chondroitin Sulfates / Q000378:metabolism*; D003412:Cricetulus; D003871:Dermatan Sulfate / Q000378:metabolism*; D004789:Enzyme Activation; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D051419:Paxillin / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D015238:Sulfotransferases / Q000235:genetics / Q000378:metabolism*; D053668:Syndecan-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D051419:Paxillin; D053668:Syndecan-1; D016222:Fibroblast Growth Factor 2; D003871:Dermatan Sulfate; D002809:Chondroitin Sulfates; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D015238:Sulfotransferases; C000606136:uronyl 2-O-sulfotransferase, mouse