Interaction of hepatocyte growth factor with heparan sulfate. Elucidation of the major heparan sulfate structural determinants.
dc.contributor.author | Lyon, Malcolm | |
dc.contributor.author | Deakin, Jon A | |
dc.contributor.author | Mizuno, K | |
dc.contributor.author | Nakamura, T | |
dc.contributor.author | Gallagher, John T | |
dc.date.accessioned | 2010-04-22T09:35:46Z | |
dc.date.available | 2010-04-22T09:35:46Z | |
dc.date.issued | 1994-04-15 | |
dc.identifier.citation | Interaction 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.issn | 0021-9258 | |
dc.identifier.pmid | 8157651 | |
dc.identifier.uri | http://hdl.handle.net/10541/97134 | |
dc.description.abstract | We 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.iso | en | en |
dc.subject.mesh | Animals | |
dc.subject.mesh | Carbohydrate Sequence | |
dc.subject.mesh | Chromatography, Affinity | |
dc.subject.mesh | Disaccharides | |
dc.subject.mesh | Fibroblasts | |
dc.subject.mesh | Heparan Sulfate Proteoglycans | |
dc.subject.mesh | Heparin | |
dc.subject.mesh | Heparitin Sulfate | |
dc.subject.mesh | Hepatocyte Growth Factor | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Liver | |
dc.subject.mesh | Molecular Sequence Data | |
dc.subject.mesh | Oligosaccharides | |
dc.subject.mesh | Proteoglycans | |
dc.subject.mesh | Rats | |
dc.subject.mesh | Recombinant Proteins | |
dc.title | Interaction of hepatocyte growth factor with heparan sulfate. Elucidation of the major heparan sulfate structural determinants. | en |
dc.type | Article | en |
dc.contributor.department | Cancer Research Campaign, Christie Hospital, Manchester, United Kingdom. | en |
dc.identifier.journal | The Journal of Biological Chemistry | en |
html.description.abstract | We 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. |