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 (Kd) 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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April 2003
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Conference Article|
April 01 2003
Hepatocyte growth factor/scatter factor and its interaction with heparan sulphate and dermatan sulphate
K. Catlow;
K. Catlow
1
*Cancer Research UK and University of Manchester Department of Medical Oncology, Christie Hospital NHS Trust, Manchester, U.K.
1To whom correspondence should be addressed (e-mail KCatlow@PICR.man.ac.uk).
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J.A. Deakin;
J.A. Deakin
*Cancer Research UK and University of Manchester Department of Medical Oncology, Christie Hospital NHS Trust, Manchester, U.K.
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M. Delehedde;
M. Delehedde
†School of Biological Sciences, University of Liverpool, Liverpool, U.K.
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D.G. Fernig;
D.G. Fernig
†School of Biological Sciences, University of Liverpool, Liverpool, U.K.
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J.T. Gallagher;
J.T. Gallagher
*Cancer Research UK and University of Manchester Department of Medical Oncology, Christie Hospital NHS Trust, Manchester, U.K.
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M.S.G. Pavão;
M.S.G. Pavão
‡Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
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M. Lyon
M. Lyon
*Cancer Research UK and University of Manchester Department of Medical Oncology, Christie Hospital NHS Trust, Manchester, U.K.
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Publisher: Portland Press Ltd
Online ISSN: 1470-8752
Print ISSN: 0300-5127
Copyright 2003 Biochemical Society
2003
Biochem Soc Trans (2003) 31 (2): 352–353.
Citation
K. Catlow, J.A. Deakin, M. Delehedde, D.G. Fernig, J.T. Gallagher, M.S.G. Pavão, M. Lyon; Hepatocyte growth factor/scatter factor and its interaction with heparan sulphate and dermatan sulphate. Biochem Soc Trans 1 April 2003; 31 (2): 352–353. doi: https://doi.org/10.1042/bst0310352
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