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Article Dans Une Revue Biochemical Journal Année : 2006

Heparan sulphate 6-O-endosulphatases: discrete in vivo activities and functional co-operativity

William C Lamanna
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Rebecca J Baldwin
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Michael Padva
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Ina Kalus
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Gerdy ten Dam
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Toin H van Kuppevelt
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John T Gallagher
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Kurt von Figura
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Thomas Dierks
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Catherine Lr Merry
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Résumé

Heparan sulphate (HS) 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 sulphated domains in the HS polymer chain. The sulphation patterning of HS is determined by a complex interplay of Golgi-located N-and O-sulphotransferases that sulphate the heparan precursor and cell surface endosulphatases that selectively remove 6-O-sulphates (6S) from mature HS chains. In the present study we generated single or dual knock out mice for the two murine endosulphatases mSulf1 and mSulf2. Detailed structural analysis of HS from mSulf1 -/-} fibroblasts showed a striking increase in 6-O-sulphation, which was not seen in mSulf2 -/-} HS. Intriguingly, the level of 6-sulphation in the double mSulf1 -/-}/2 -/-} HS was significantly higher than that in the mSulf1 -/-} counterpart. These data imply that mSulf1 and mSulf2 are functionally cooperative. Unlike their avian orthologues, mammalian Sulf activities are not restricted to the highly sulphated S-domains of HS. Mitogenesis assays with FGF2 revealed that Sulf activity dampens the activating potential of newly-synthesised HS suggesting an important role for these enzymes in cell growth regulation in embryonic and adult tissues.

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Dates et versions

hal-00478612 , version 1 (30-04-2010)

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William C Lamanna, Rebecca J Baldwin, Michael Padva, Ina Kalus, Gerdy ten Dam, et al.. Heparan sulphate 6-O-endosulphatases: discrete in vivo activities and functional co-operativity. Biochemical Journal, 2006, 400 (1), pp.63-73. ⟨10.1042/BJ20060848⟩. ⟨hal-00478612⟩

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