Hepatocyte growth factor/scatter factor and its interaction with heparan sulphate and dermatan sulphate |
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Authors: | Catlow K Deakin J A Delehedde M Fernig D G Gallagher J T Pavão M S G Lyon M |
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Institution: | Cancer Research UK and University of Manchester Department of Medical Oncology, Christie Hospital NHS Trust, Manchester, U.K. KCatlow@PICR.man.ac.uk |
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Abstract: | 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. |
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