Disease relevance of Hs2st1

• In the study presented here, we further investigated the substrate specificity of the mouse mastocytoma 2-OST [1].

High impact information on Hs2st1

• Analysis of kidney development in Hs2st mutants reveals that the gene is not required for two early events-ureteric bud outgrowth from the Wolffian duct and initial induction of Pax-2 expression in the metanephric mesenchyme [2].
• Because 2-O-sulfation has been shown to influence the functional interactions of ligands with heparan sulfate in vitro, we discuss the possibility that the Hs2st mutant phenotype is a consequence of compromised interactions between growth factors and their signal-transducing receptors [2].
• Enzyme interactions in heparan sulfate biosynthesis: uronosyl 5-epimerase and 2-O-sulfotransferase interact in vivo [3].
• 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 [4].
• In agreement with these results, the 2-OST was found to have a approximately 5-fold higher affinity for iduronic acid-containing substrate disaccharide units (K(m) approximately 3.7 microM) than for glucuronic acid-containing substrate disaccharide units (K(m) approximately 19.3 microM) [1].

Biological context of Hs2st1

• Comparison of the fates of cortical cells born on E13 and E15 in Hs2st(-/-) mutant and wildtype littermate embryos revealed no differences in the pattern of cell migration [5].

Anatomical context of Hs2st1

• The gene encoding heparan sulphate 2-sulphotransferase (Hs2st) is expressed in embryonic cortex and histological analysis of mice homozygous for a null mutation in Hs2st indicated a reduction in the thickness of the embryonic cerebral cortex [5].
• We suggest that (1) Hs2st and Hs6st1 are each deployed to generate distinct patterns of heparan sulfation on RGCs and at the optic chiasm and (2) this differential sulfation directs retinal axons through the chiasm, at least in part by modulating the response of the navigating growth cone to Slit proteins [6].

Associations of Hs2st1 with chemical compounds

• 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 [7].

Other interactions of Hs2st1

• We identified different axon navigation phenotypes in two heparan sulfate sulfotransferase (Hst) mutant embryos, Hs2st-/- and Hs6st1-/-, each lacking an enzyme that catalyzes a particular HSPG modification [6].

References