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dc.contributor.authorLyon, Malcolm
dc.contributor.authorDeakin, Jon A
dc.contributor.authorMizuno, K
dc.contributor.authorNakamura, T
dc.contributor.authorGallagher, John T
dc.date.accessioned2010-04-22T09:35:46Z
dc.date.available2010-04-22T09:35:46Z
dc.date.issued1994-04-15
dc.identifier.citationInteraction of hepatocyte growth factor with heparan sulfate. Elucidation of the major heparan sulfate structural determinants. 1994, 269 (15):11216-23 J. Biol. Chem.en
dc.identifier.issn0021-9258
dc.identifier.pmid8157651
dc.identifier.urihttp://hdl.handle.net/10541/97134
dc.description.abstractWe have demonstrated by affinity chromatography that hepatocyte growth factor (HGF) binds strongly to heparan sulfate (HS). This substantiates previous suggestions that cell-surface heparan sulfate proteoglycans constitute the so-called low affinity cellular binding sites for HGF. Using a recombinant human HGF affinity column, we have analyzed the effects of various specific chemical and enzymatic modifications/depolymerizations of HS on its affinity in order to elucidate the polysaccharide structural determinants. Interaction is shown to be only slightly affected by digestion with heparinase I or III or by replacement of N-sulfates with N-acetyl groups. This suggests a specific role for sulfated domains containing nonsulfated IdceA residues, with only a small contribution from N-sulfates and IdceA(2-OSO3) residues. In addition, disaccharide analyses of various HGF-binding oligosaccharides indicate that affinity is more closely associated with 6-O-sulfation of GlcNSO3 residues than with sulfation at any other position. Although interaction can be demonstrated with heparinase III-resistant oligosaccharides as small as hexasaccharides, the highest affinity was found with oligosaccharides containing a minimum of 10-12 monosaccharides. The structural specificity of the HGF-HS interaction is thus shown to be radically different from that previously described for the basic fibroblast growth factor-HS interaction.
dc.language.isoenen
dc.subject.meshAnimals
dc.subject.meshCarbohydrate Sequence
dc.subject.meshChromatography, Affinity
dc.subject.meshDisaccharides
dc.subject.meshFibroblasts
dc.subject.meshHeparan Sulfate Proteoglycans
dc.subject.meshHeparin
dc.subject.meshHeparitin Sulfate
dc.subject.meshHepatocyte Growth Factor
dc.subject.meshHumans
dc.subject.meshLiver
dc.subject.meshMolecular Sequence Data
dc.subject.meshOligosaccharides
dc.subject.meshProteoglycans
dc.subject.meshRats
dc.subject.meshRecombinant Proteins
dc.titleInteraction of hepatocyte growth factor with heparan sulfate. Elucidation of the major heparan sulfate structural determinants.en
dc.typeArticleen
dc.contributor.departmentCancer Research Campaign, Christie Hospital, Manchester, United Kingdom.en
dc.identifier.journalThe Journal of Biological Chemistryen
html.description.abstractWe have demonstrated by affinity chromatography that hepatocyte growth factor (HGF) binds strongly to heparan sulfate (HS). This substantiates previous suggestions that cell-surface heparan sulfate proteoglycans constitute the so-called low affinity cellular binding sites for HGF. Using a recombinant human HGF affinity column, we have analyzed the effects of various specific chemical and enzymatic modifications/depolymerizations of HS on its affinity in order to elucidate the polysaccharide structural determinants. Interaction is shown to be only slightly affected by digestion with heparinase I or III or by replacement of N-sulfates with N-acetyl groups. This suggests a specific role for sulfated domains containing nonsulfated IdceA residues, with only a small contribution from N-sulfates and IdceA(2-OSO3) residues. In addition, disaccharide analyses of various HGF-binding oligosaccharides indicate that affinity is more closely associated with 6-O-sulfation of GlcNSO3 residues than with sulfation at any other position. Although interaction can be demonstrated with heparinase III-resistant oligosaccharides as small as hexasaccharides, the highest affinity was found with oligosaccharides containing a minimum of 10-12 monosaccharides. The structural specificity of the HGF-HS interaction is thus shown to be radically different from that previously described for the basic fibroblast growth factor-HS interaction.


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