Heparan sulfate 6-O-endosulfatases: discrete in vivo activities and functional co-operativity.

2.50
Hdl Handle:
http://hdl.handle.net/10541/72694
Title:
Heparan sulfate 6-O-endosulfatases: discrete in vivo activities and functional co-operativity.
Authors:
Lamanna, William C; Baldwin, Rebecca J; Padva, Michael; Kalus, Ina; Ten Dam, Gerdy; Van Kuppevelt, Toin H; Gallagher, John T; Von Figura, Kurt; Dierks, Thomas; Merry, Catherine L R
Abstract:
HS (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.
Affiliation:
Department of Chemistry, Biochemistry I, Bielefeld University, Universitätsstrasse 25, 33615 Bielefeld, Germany.
Citation:
Heparan sulfate 6-O-endosulfatases: discrete in vivo activities and functional co-operativity. 2006, 400 (1):63-73 Biochem. J.
Journal:
The Biochemical Journal
Issue Date:
15-Nov-2006
URI:
http://hdl.handle.net/10541/72694
DOI:
10.1042/BJ20060848
PubMed ID:
16901266
Type:
Article
Language:
en
ISSN:
1470-8728
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
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.en
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

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