The molecular phenotype of heparan sulfate in the Hs2st-/- mutant mouse.
AuthorsMerry, Catherine L R
Bullock, Simon L
Swan, Daniel C
Backen, Alison C
Beddington, Rosa S
Wilson, Valerie A
Gallagher, John T
AffiliationCancer Research Campaign Department of Medical Oncology, Christie Hospital NHS Trust, Manchester M20 4BX, United Kingdom. firstname.lastname@example.org
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AbstractHeparan sulfate (HS) is a co-receptor for a number of growth factors, morphogens, and adhesion proteins. HS biosynthetic modifications may determine the strength and outcome of HS-ligand interactions. We previously described the phenotype of mice with a gene-trap mutation in Hs2st, encoding the key HS 2-O-sulfotransferase enzyme in HS polymer modification. In contrast to the early developmental failure of embryos lacking HS, the onset of abnormalities in the Hs2st(-/-) mice occurs only after midgestation, the most dramatic being the complete failure of kidney development. Uronate 2-O-sulfates were not detected in the mutant HS, indicating a complete loss of function of Hs2st. However, the domain structure of the mutant HS is conserved, and compensatory increases in N- and 6-O-sulfation maintain the overall charge density. The apparent affinities of the mutant HS for hepatocyte growth factor/scatter factor and fibronectin were unchanged but were reduced for fibroblast growth factor-1 and -2. Surprisingly, the Hs2st(-/-) cells were able to mount an apparently normal signaling response to fibroblast growth factor-1 and -2 as well as to hepatocyte growth factor/scatter factor.
CitationThe molecular phenotype of heparan sulfate in the Hs2st-/- mutant mouse. 2001, 276 (38):35429-34 J. Biol. Chem.
JournalThe Journal of Biological Chemistry
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