Heparan sulfate 6-O-endosulfatases: discrete in vivo activities and functional co-operativity.
Authors
Lamanna, William CBaldwin, 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
Affiliation
Department of Chemistry, Biochemistry I, Bielefeld University, Universitätsstrasse 25, 33615 Bielefeld, Germany.Issue Date
2006-11-15
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Show full item recordAbstract
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.Citation
Heparan sulfate 6-O-endosulfatases: discrete in vivo activities and functional co-operativity. 2006, 400 (1):63-73 Biochem. J.Journal
The Biochemical JournalDOI
10.1042/BJ20060848PubMed ID
16901266Type
ArticleLanguage
enISSN
1470-8728ae974a485f413a2113503eed53cd6c53
10.1042/BJ20060848
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