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dc.contributor.authorLamanna, William C
dc.contributor.authorBaldwin, Rebecca J
dc.contributor.authorPadva, Michael
dc.contributor.authorKalus, Ina
dc.contributor.authorTen Dam, Gerdy
dc.contributor.authorVan Kuppevelt, Toin H
dc.contributor.authorGallagher, John T
dc.contributor.authorVon Figura, Kurt
dc.contributor.authorDierks, Thomas
dc.contributor.authorMerry, Catherine L R
dc.date.accessioned2009-07-07T09:40:06Z
dc.date.available2009-07-07T09:40:06Z
dc.date.issued2006-11-15
dc.identifier.citationHeparan sulfate 6-O-endosulfatases: discrete in vivo activities and functional co-operativity. 2006, 400 (1):63-73 Biochem. J.en
dc.identifier.issn1470-8728
dc.identifier.pmid16901266
dc.identifier.doi10.1042/BJ20060848
dc.identifier.urihttp://hdl.handle.net/10541/72694
dc.description.abstractHS (heparan sulfate) is essential for normal embryonic development. This requirement is due to the obligatory role for HS in the signalling pathways of many growth factors and morphogens that bind to sulfated domains in the HS polymer chain. The sulfation patterning of HS is determined by a complex interplay of Golgi-located N- and O-sulfotransferases which sulfate the heparan precursor and cell surface endosulfatases that selectively remove 6-O-sulfates from mature HS chains. In the present study we generated single or double knock-out mice for the two murine endosulfatases mSulf1 and mSulf2. Detailed structural analysis of HS from mSulf1-/- fibroblasts showed a striking increase in 6-O-sulfation, which was not seen in mSulf2-/- HS. Intriguingly, the level of 6-O-sulfation in the double mSulf1-/-/2-/- HS was significantly higher than that observed in the mSulf1-/- counterpart. These data imply that mSulf1 and mSulf2 are functionally co-operative. Unlike their avian orthologues, mammalian Sulf activities are not restricted to the highly sulfated S-domains of HS. Mitogenesis assays with FGF2 (fibroblast growth factor 2) revealed that Sulf activity decreases the activating potential of newly-synthesized HS, suggesting an important role for these enzymes in cell growth regulation in embryonic and adult tissues.
dc.language.isoenen
dc.subject.meshAnimals
dc.subject.meshAntibodies
dc.subject.meshCell Proliferation
dc.subject.meshCells, Cultured
dc.subject.meshDisaccharides
dc.subject.meshEpitopes
dc.subject.meshFemale
dc.subject.meshFibroblast Growth Factor 2
dc.subject.meshFibroblasts
dc.subject.meshGenotype
dc.subject.meshHeparitin Sulfate
dc.subject.meshMale
dc.subject.meshMice
dc.subject.meshMice, Inbred C57BL
dc.subject.meshMice, Inbred Strains
dc.subject.meshMice, Knockout
dc.subject.meshMolecular Structure
dc.subject.meshOligosaccharides
dc.subject.meshSulfatases
dc.subject.meshSulfates
dc.subject.meshSulfotransferases
dc.titleHeparan sulfate 6-O-endosulfatases: discrete in vivo activities and functional co-operativity.en
dc.typeArticleen
dc.contributor.departmentDepartment of Chemistry, Biochemistry I, Bielefeld University, Universitätsstrasse 25, 33615 Bielefeld, Germany.en
dc.identifier.journalThe Biochemical Journalen
refterms.dateFOA2020-04-27T12:52:55Z
html.description.abstractHS (heparan sulfate) is essential for normal embryonic development. This requirement is due to the obligatory role for HS in the signalling pathways of many growth factors and morphogens that bind to sulfated domains in the HS polymer chain. The sulfation patterning of HS is determined by a complex interplay of Golgi-located N- and O-sulfotransferases which sulfate the heparan precursor and cell surface endosulfatases that selectively remove 6-O-sulfates from mature HS chains. In the present study we generated single or double knock-out mice for the two murine endosulfatases mSulf1 and mSulf2. Detailed structural analysis of HS from mSulf1-/- fibroblasts showed a striking increase in 6-O-sulfation, which was not seen in mSulf2-/- HS. Intriguingly, the level of 6-O-sulfation in the double mSulf1-/-/2-/- HS was significantly higher than that observed in the mSulf1-/- counterpart. These data imply that mSulf1 and mSulf2 are functionally co-operative. Unlike their avian orthologues, mammalian Sulf activities are not restricted to the highly sulfated S-domains of HS. Mitogenesis assays with FGF2 (fibroblast growth factor 2) revealed that Sulf activity decreases the activating potential of newly-synthesized HS, suggesting an important role for these enzymes in cell growth regulation in embryonic and adult tissues.


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