2.50
Hdl Handle:
http://hdl.handle.net/10541/85732
Title:
The molecular phenotype of heparan sulfate in the Hs2st-/- mutant mouse.
Authors:
Merry, Catherine L R; Bullock, Simon L; Swan, Daniel C; Backen, Alison C; Lyon, Malcolm; Beddington, Rosa S; Wilson, Valerie A; Gallagher, John T
Abstract:
Heparan 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.
Affiliation:
Cancer Research Campaign Department of Medical Oncology, Christie Hospital NHS Trust, Manchester M20 4BX, United Kingdom. cmerry@picr.man.ac.uk
Citation:
The molecular phenotype of heparan sulfate in the Hs2st-/- mutant mouse. 2001, 276 (38):35429-34 J. Biol. Chem.
Journal:
The Journal of Biological Chemistry
Issue Date:
21-Sep-2001
URI:
http://hdl.handle.net/10541/85732
DOI:
10.1074/jbc.M100379200
PubMed ID:
11457822
Type:
Article
Language:
en
ISSN:
0021-9258
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorMerry, Catherine L Ren
dc.contributor.authorBullock, Simon Len
dc.contributor.authorSwan, Daniel Cen
dc.contributor.authorBacken, Alison Cen
dc.contributor.authorLyon, Malcolmen
dc.contributor.authorBeddington, Rosa Sen
dc.contributor.authorWilson, Valerie Aen
dc.contributor.authorGallagher, John Ten
dc.date.accessioned2009-11-10T10:06:22Z-
dc.date.available2009-11-10T10:06:22Z-
dc.date.issued2001-09-21-
dc.identifier.citationThe molecular phenotype of heparan sulfate in the Hs2st-/- mutant mouse. 2001, 276 (38):35429-34 J. Biol. Chem.en
dc.identifier.issn0021-9258-
dc.identifier.pmid11457822-
dc.identifier.doi10.1074/jbc.M100379200-
dc.identifier.urihttp://hdl.handle.net/10541/85732-
dc.description.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.en
dc.language.isoenen
dc.subject.meshAnimals-
dc.subject.meshDisaccharides-
dc.subject.meshFibroblast Growth Factors-
dc.subject.meshHeparitin Sulfate-
dc.subject.meshHepatocyte Growth Factor-
dc.subject.meshHydrolysis-
dc.subject.meshMice-
dc.subject.meshMice, Mutant Strains-
dc.subject.meshNitrous Acid-
dc.subject.meshPhenotype-
dc.subject.meshPolysaccharide-Lyases-
dc.subject.meshSulfotransferases-
dc.titleThe molecular phenotype of heparan sulfate in the Hs2st-/- mutant mouse.en
dc.typeArticleen
dc.contributor.departmentCancer Research Campaign Department of Medical Oncology, Christie Hospital NHS Trust, Manchester M20 4BX, United Kingdom. cmerry@picr.man.ac.uken
dc.identifier.journalThe Journal of Biological Chemistryen

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