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Uronyl 2-O sulfotransferase potentiates Fgf2-induced cell migration
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
2015 (English)In: Journal of Cell Science, ISSN 0021-9533, E-ISSN 1477-9137, Vol. 128, no 3, 460-471 p.Article in journal (Refereed) Published
Abstract [en]

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 [-4GlcUA beta 1-3-GalNAc-beta 1-] and [-4IdoUA alpha 1-3-GalNAc-beta 1-], which can be sulfated. Uronyl 2-O-sulfotransferase (Ust) introduces sulfation at the C2 of IdoUA and GlcUA resulting in over-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/DS 2-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.

Place, publisher, year, edition, pages
2015. Vol. 128, no 3, 460-471 p.
Keyword [en]
Chondroitin sulfate, Dermatan sulfate, 2-O Sulfation, Uronyl 2-O sulfotransferase, Fibroblast growth factor 2, Cell migration
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
URN: urn:nbn:se:uu:diva-246827DOI: 10.1242/jcs.152660ISI: 000349017900005OAI: oai:DiVA.org:uu-246827DiVA: diva2:795133
Available from: 2015-03-13 Created: 2015-03-10 Last updated: 2017-12-04Bibliographically approved

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Spillmann, Dorothe

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