Hepatocyte growth factor/scatter factor binds with high affinity to dermatan sulfate.
AffiliationCancer 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
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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.
CitationHepatocyte growth factor/scatter factor binds with high affinity to dermatan sulfate. 1998, 273 (1):271-8 J. Biol. Chem.
JournalThe Journal of biological chemistry
- The binding properties of minimal oligosaccharides reveal a common heparan sulfate/dermatan sulfate-binding site in hepatocyte growth factor/scatter factor that can accommodate a wide variety of sulfation patterns.
- Authors: Deakin JA, Blaum BS, Gallagher JT, Uhrín D, Lyon M
- Issue date: 2009 Mar 6
- Hepatocyte growth factor/scatter factor and its interaction with heparan sulphate and dermatan sulphate.
- Authors: Catlow K, Deakin JA, Delehedde M, Fernig DG, Gallagher JT, Pavão MS, Lyon M
- Issue date: 2003 Apr
- Interactions of hepatocyte growth factor/scatter factor with various glycosaminoglycans reveal an important interplay between the presence of iduronate and sulfate density.
- Authors: Catlow KR, Deakin JA, Wei Z, Delehedde M, Fernig DG, Gherardi E, Gallagher JT, Pavão MS, Lyon M
- Issue date: 2008 Feb 29
- Hepatocyte growth factor/scatter factor binds to small heparin-derived oligosaccharides and stimulates the proliferation of human HaCaT keratinocytes.
- Authors: Delehedde M, Lyon M, Vidyasagar R, McDonnell TJ, Fernig DG
- Issue date: 2002 Apr 5
- Interaction of hepatocyte growth factor with heparan sulfate. Elucidation of the major heparan sulfate structural determinants.
- Authors: Lyon M, Deakin JA, Mizuno K, Nakamura T, Gallagher JT
- Issue date: 1994 Apr 15