Differential regulation of hepatocyte growth factor/scatter factor by cell surface proteoglycans and free glycosaminoglycan chains.

2.50
Hdl Handle:
http://hdl.handle.net/10541/90769
Title:
Differential regulation of hepatocyte growth factor/scatter factor by cell surface proteoglycans and free glycosaminoglycan chains.
Authors:
Deakin, Jon A; Lyon, Malcolm
Abstract:
Hepatocyte growth factor interacts with both heparan and dermatan sulphates, in addition to its specific signalling receptor, Met. However, the extent of glycosaminoglycan involvement in its biological activity remains uncertain. We have investigated the effects of exogenous glycosaminoglycan addition upon hepatocyte growth factor-stimulated motility of Madin-Darby canine kidney cells. Exogenous heparan/dermatan sulphate chains behave similarly as either potentiators or inhibitors of cell motility (depending upon the assay). Specific heparan sulphate oligosaccharides, of octasaccharide or larger, elicit similar effects, though with reduced potency. Additionally we have investigated the motility of cells made completely deficient in functional proteoglycans by metabolic inhibition of glycosaminoglycan sulphation, using chlorate. Such cells are completely unresponsive to hepatocyte growth factor, both in terms of downstream phosphorylation of mitogen-activated protein kinase and actual cell motility, though they do remain responsive to phorbol ester. Interestingly, although cell responsiveness to hepatocyte growth factor is not restored by exogenous heparan/dermatan sulphate chains, it is by an immobilised heparan sulphate proteoglycan substratum. These findings suggest that hepatocyte growth factor activity is not only critically dependent upon the presence of glycosaminoglycan, but specifically requires an intact proteoglycan structure located in close apposition to cell surface Met.
Affiliation:
Cancer Research Campaign Department of Medical Oncology, University of Manchester, Christie Hospital NHS Trust, Wilmslow Road, Manchester M20 4BX, UK.
Citation:
Differential regulation of hepatocyte growth factor/scatter factor by cell surface proteoglycans and free glycosaminoglycan chains. 1999, 112 ( Pt 12):1999-2009 J. Cell. Sci.
Journal:
Journal of Cell Science
Issue Date:
Jun-1999
URI:
http://hdl.handle.net/10541/90769
PubMed ID:
10341217
Type:
Article
Language:
en
ISSN:
0021-9533
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorDeakin, Jon Aen
dc.contributor.authorLyon, Malcolmen
dc.date.accessioned2010-01-28T13:52:59Z-
dc.date.available2010-01-28T13:52:59Z-
dc.date.issued1999-06-
dc.identifier.citationDifferential regulation of hepatocyte growth factor/scatter factor by cell surface proteoglycans and free glycosaminoglycan chains. 1999, 112 ( Pt 12):1999-2009 J. Cell. Sci.en
dc.identifier.issn0021-9533-
dc.identifier.pmid10341217-
dc.identifier.urihttp://hdl.handle.net/10541/90769-
dc.description.abstractHepatocyte growth factor interacts with both heparan and dermatan sulphates, in addition to its specific signalling receptor, Met. However, the extent of glycosaminoglycan involvement in its biological activity remains uncertain. We have investigated the effects of exogenous glycosaminoglycan addition upon hepatocyte growth factor-stimulated motility of Madin-Darby canine kidney cells. Exogenous heparan/dermatan sulphate chains behave similarly as either potentiators or inhibitors of cell motility (depending upon the assay). Specific heparan sulphate oligosaccharides, of octasaccharide or larger, elicit similar effects, though with reduced potency. Additionally we have investigated the motility of cells made completely deficient in functional proteoglycans by metabolic inhibition of glycosaminoglycan sulphation, using chlorate. Such cells are completely unresponsive to hepatocyte growth factor, both in terms of downstream phosphorylation of mitogen-activated protein kinase and actual cell motility, though they do remain responsive to phorbol ester. Interestingly, although cell responsiveness to hepatocyte growth factor is not restored by exogenous heparan/dermatan sulphate chains, it is by an immobilised heparan sulphate proteoglycan substratum. These findings suggest that hepatocyte growth factor activity is not only critically dependent upon the presence of glycosaminoglycan, but specifically requires an intact proteoglycan structure located in close apposition to cell surface Met.en
dc.language.isoenen
dc.subject.meshAbsorption-
dc.subject.meshAnimals-
dc.subject.meshCell Line-
dc.subject.meshChlorates-
dc.subject.meshDogs-
dc.subject.meshGlycosaminoglycans-
dc.subject.meshHeparitin Sulfate-
dc.subject.meshHepatocyte Growth Factor-
dc.subject.meshHumans-
dc.subject.meshKidney-
dc.subject.meshMembrane Proteins-
dc.subject.meshOligosaccharides-
dc.subject.meshProteoglycans-
dc.subject.meshRecombinant Proteins-
dc.subject.meshReference Values-
dc.titleDifferential regulation of hepatocyte growth factor/scatter factor by cell surface proteoglycans and free glycosaminoglycan chains.en
dc.typeArticleen
dc.contributor.departmentCancer Research Campaign Department of Medical Oncology, University of Manchester, Christie Hospital NHS Trust, Wilmslow Road, Manchester M20 4BX, UK.en
dc.identifier.journalJournal of Cell Scienceen
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