Interaction of hepatocyte growth factor with heparan sulfate. Elucidation of the major heparan sulfate structural determinants.

2.50
Hdl Handle:
http://hdl.handle.net/10541/97134
Title:
Interaction of hepatocyte growth factor with heparan sulfate. Elucidation of the major heparan sulfate structural determinants.
Authors:
Lyon, Malcolm; Deakin, Jon A; Mizuno, K; Nakamura, T; Gallagher, John T
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.
Affiliation:
Cancer Research Campaign, Christie Hospital, Manchester, United Kingdom.
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.
Journal:
The Journal of Biological Chemistry
Issue Date:
15-Apr-1994
URI:
http://hdl.handle.net/10541/97134
PubMed ID:
8157651
Type:
Article
Language:
en
ISSN:
0021-9258
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorLyon, Malcolmen
dc.contributor.authorDeakin, Jon Aen
dc.contributor.authorMizuno, Ken
dc.contributor.authorNakamura, Ten
dc.contributor.authorGallagher, John Ten
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.en
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

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