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Heparan sulfate 2-O-sulfotransferase (Hs2st) and mouse development

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Abstract

Heparan sulphate 2-O-sulphotransferase (Hs2st) acts at an intermediate stage in the pathway of biosynthesis of heparan sulphate (HS), catalysing the transfer of sulphate from 3′-phosphoadenosine-5′-phosphosulfate (PAPS) to the C2-position of selected hexuronic acid residues within the maturing HS chain. It is well established that 2-O-sulphation within HS, particularly of iduronate residues, is essential for HS to participate in a variety of high-affinity ligand-binding interactions. HS plays a central role in embryonic development and cellular function, modulating the activities of an extensive range of growth factors. Interestingly, in contrast to the early failure of embryos entirely lacking HS, Hs2st −/− mice survive until birth, but die perinatally due to a complete failure of kidney formation. The phenotype of Hs2st −/− mutant kidneys suggests that signalling between two tissues, ureteric bud and metanephric mesenchyme, is disrupted. We discuss candidate signalling molecules that may mediate this interaction. The HS generated by these mice lacks 2-O-sulphate groups but is extensively modified above wild type levels by O-sulphation at C-6 of glucosamine-N-sulfate (GlcNS) residues. We will discuss the potentially altered role of this atypical HS in growth factor signalling. Published in 2003.

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Authors and Affiliations

  1. Institute for Stem Cell Research, University of Edinburgh, Edinburgh, EH9 3JQ, UK

    Valerie A. Wilson

  2. Cancer Research UK Department of Medical Oncology, Christie Hospital NHS Trust, Manchester, M20 4BX, UK

    John T. Gallagher & Catherine L.R. Merry

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  1. Valerie A. Wilson
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Wilson, V.A., Gallagher, J.T. & Merry, C.L. Heparan sulfate 2-O-sulfotransferase (Hs2st) and mouse development. Glycoconj J 19, 347–354 (2002). https://doi.org/10.1023/A:1025325222530

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