Hepatocyte growth factor/scatter factor and its interaction with heparan sulphate and dermatan sulphate.
Catlow, Krista R Deakin, Jon A Delehedde, Maryse Fernig, D G Gallagher, John T Pavão, M S G Lyon, Malcolm
Catlow, Krista R
Deakin, Jon A
Delehedde, Maryse
Fernig, D G
Gallagher, John T
Pavão, M S G
Lyon, Malcolm
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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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Date
2003-04
Publisher
Collections
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Type
Article
Citation
Hepatocyte growth factor/scatter factor and its interaction with heparan sulphate and dermatan sulphate. 2003, 31 (2):352-3 Biochem. Soc. Trans.