Hepatocyte growth factor/scatter factor binds with high affinity to dermatan sulfate.
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.
Lyon
M
M
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
Deakin
J A
JA
Rahmoune
H
H
Fernig
D G
DG
Nakamura
T
T
Gallagher
J T
JT
D016475:3T3 Cells; D000818:Animals; D001667:Binding, Competitive; D002236:Carbohydrate Conformation; D002460:Cell Line; D003871:Dermatan Sulfate / Q000378:metabolism*; D004285:Dogs; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D009844:Oligosaccharides / Q000737:chemistry; D011485:Protein Binding
D009844:Oligosaccharides; D003871:Dermatan Sulfate; D017228:Hepatocyte Growth Factor