Hepatocyte growth factor/scatter factor and its interaction with heparan sulphate and dermatan sulphate.
Hepatocyte growth factor (HGF)/scatter factor (SF) is a unique growth factor, in that it binds both heparan sulphate (HS) and dermatan sulphate (DS). The sequences in HS and DS that specifically interact with and modulate HGF/SF activity have not yet been fully identified. Ascidian DS, which uniquely possesses O-sulphation at C-6 (and not C-4) of its N -acetylgalactosamine unit, was analysed for HGF/SF-binding activity in the biosensor. The kinetic analysis revealed a strong, biologically relevant interaction with an equilibrium dissociation constant ( K (d)) of approx. 1 nM. An Erk activation assay also demonstrated stimulation of the MAP kinase pathway downstream of the Met receptor following addition of both HGF/SF and ascidian DS to the glycosaminoglycan-deficient CHO-745 mutant cell line. Furthermore, the activation of Met and the MAP kinase pathway by HGF/SF and ascidian DS leads to a cellular response in the form of migration.
Catlow
K
K
Cancer Research UK and University of Manchester Department of Medical Oncology, Christie Hospital NHS Trust, Manchester, U.K. KCatlow@PICR.man.ac.uk
Deakin
J A
JA
Delehedde
M
M
Fernig
D G
DG
Gallagher
J T
JT
Pavão
M S G
MS
Lyon
M
M
D000818:Animals; D003871:Dermatan Sulfate / Q000378:metabolism*; D006497:Heparan Sulfate / Q000378:metabolism*; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D011485:Protein Binding; D015398:Signal Transduction
D003871:Dermatan Sulfate; D006497:Heparan Sulfate; D017228:Hepatocyte Growth Factor