Hepatocyte growth factor/scatter factor binds with high affinity to dermatan sulfate.

2.50
Hdl Handle:
http://hdl.handle.net/10541/92922
Title:
Hepatocyte growth factor/scatter factor binds with high affinity to dermatan sulfate.
Authors:
Lyon, Malcolm; Deakin, Jon A; Rahmoune, H; Fernig, D G; Nakamura, T; Gallagher, John T
Abstract:
We have demonstrated by affinity chromatography that hepatocyte growth factor/scatter factor (HGF/SF) binds strongly to dermatan sulfate (DS), with a similar ionic strength dependence to that previously seen with heparan sulfate (HS). Analysis of binding kinetics on a biosensor yields an equilibrium dissociation constant, KD, of 19.7 nM. This corresponds to a 10-100-fold weaker interaction than that with HS, primarily due to a faster dissociation rate of the complex. The smallest DS oligosaccharide with significant affinity for HGF/SF by affinity chromatography appears to be an octasaccharide. A sequence comprising unsulfated iduronate residues in combination with 4-O-sulfated N-acetylgalactosamine is sufficient for high affinity binding. The presence of 2-O-sulfation on the iduronate residues does not appear to be inhibitory. These observations concur with our previous suggestions, from analyses of HS binding (Lyon, M., Deakin, J. A., Mizuno, K., Nakamura, T., and Gallagher, J.T. (1994) J. Biol. Chem. 269, 11216-11223), that N-sulfation of hexosamines and 2-O-sulfation of iduronates are not absolute requirements for glycosaminoglycan binding to HGF/SF. This is the first described example of a high affinity interaction between a growth factor and DS, and is likely to have significant implications for the biological activity of this paracrine-acting factor.
Affiliation:
Cancer Research Campaign & University of Manchester, Department of Medical Oncology, Christie Hospital National Health Service Trust, Manchester M20 4BX, United Kingdom. MLyon@picr.man.ac.uk
Citation:
Hepatocyte growth factor/scatter factor binds with high affinity to dermatan sulfate. 1998, 273 (1):271-8 J. Biol. Chem.
Journal:
The Journal of biological chemistry
Issue Date:
2-Jan-1998
URI:
http://hdl.handle.net/10541/92922
PubMed ID:
9417075
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.authorRahmoune, Hen
dc.contributor.authorFernig, D Gen
dc.contributor.authorNakamura, Ten
dc.contributor.authorGallagher, John Ten
dc.date.accessioned2010-02-24T13:54:42Z-
dc.date.available2010-02-24T13:54:42Z-
dc.date.issued1998-01-02-
dc.identifier.citationHepatocyte growth factor/scatter factor binds with high affinity to dermatan sulfate. 1998, 273 (1):271-8 J. Biol. Chem.en
dc.identifier.issn0021-9258-
dc.identifier.pmid9417075-
dc.identifier.urihttp://hdl.handle.net/10541/92922-
dc.description.abstractWe have demonstrated by affinity chromatography that hepatocyte growth factor/scatter factor (HGF/SF) binds strongly to dermatan sulfate (DS), with a similar ionic strength dependence to that previously seen with heparan sulfate (HS). Analysis of binding kinetics on a biosensor yields an equilibrium dissociation constant, KD, of 19.7 nM. This corresponds to a 10-100-fold weaker interaction than that with HS, primarily due to a faster dissociation rate of the complex. The smallest DS oligosaccharide with significant affinity for HGF/SF by affinity chromatography appears to be an octasaccharide. A sequence comprising unsulfated iduronate residues in combination with 4-O-sulfated N-acetylgalactosamine is sufficient for high affinity binding. The presence of 2-O-sulfation on the iduronate residues does not appear to be inhibitory. These observations concur with our previous suggestions, from analyses of HS binding (Lyon, M., Deakin, J. A., Mizuno, K., Nakamura, T., and Gallagher, J.T. (1994) J. Biol. Chem. 269, 11216-11223), that N-sulfation of hexosamines and 2-O-sulfation of iduronates are not absolute requirements for glycosaminoglycan binding to HGF/SF. This is the first described example of a high affinity interaction between a growth factor and DS, and is likely to have significant implications for the biological activity of this paracrine-acting factor.en
dc.language.isoenen
dc.subject.mesh3T3 Cells-
dc.subject.meshAnimals-
dc.subject.meshBinding, Competitive-
dc.subject.meshCarbohydrate Conformation-
dc.subject.meshCell Line-
dc.subject.meshDermatan Sulfate-
dc.subject.meshDogs-
dc.subject.meshHepatocyte Growth Factor-
dc.subject.meshHumans-
dc.subject.meshKinetics-
dc.subject.meshMice-
dc.subject.meshMice, Inbred BALB C-
dc.subject.meshOligosaccharides-
dc.subject.meshProtein Binding-
dc.titleHepatocyte growth factor/scatter factor binds with high affinity to dermatan sulfate.en
dc.typeArticleen
dc.contributor.departmentCancer Research Campaign & University of Manchester, Department of Medical Oncology, Christie Hospital National Health Service Trust, Manchester M20 4BX, United Kingdom. MLyon@picr.man.ac.uken
dc.identifier.journalThe Journal of biological chemistryen
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