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. email@example.com
MetadataShow full item record
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
- Heparan Sulfate Sulfation by Hs2st Restricts Astroglial Precursor Somal Translocation in Developing Mouse Forebrain by a Non-Cell-Autonomous Mechanism.
- Authors: Clegg JM, Parkin HM, Mason JO, Pratt T
- Issue date: 2019 Feb 20
- 2-O Heparan Sulfate Sulfation by Hs2st Is Required for Erk/Mapk Signalling Activation at the Mid-Gestational Mouse Telencephalic Midline.
- Authors: Chan WK, Howe K, Clegg JM, Guimond SE, Price DJ, Turnbull JE, Pratt T
- Issue date: 2015
- Role of heparan sulfate-2-O-sulfotransferase in the mouse.
- Authors: Merry CL, Wilson VA
- Issue date: 2002 Dec 19
- Heparan sulfate 2-O-sulfotransferase (Hs2st) and mouse development.
- Authors: Wilson VA, Gallagher JT, Merry CL
- Issue date: 2002 May-Jun
- Specific and flexible roles of heparan sulfate modifications in Drosophila FGF signaling.
- Authors: Kamimura K, Koyama T, Habuchi H, Ueda R, Masu M, Kimata K, Nakato H
- Issue date: 2006 Sep 11