The Mode of Action of Heparan and Dermatan Sulfates in the Regulation of Hepatocyte Growth Factor/Scatter Factor*

@article{Lyon2002TheMO,
  title={The Mode of Action of Heparan and Dermatan Sulfates in the Regulation of Hepatocyte Growth Factor/Scatter Factor*},
  author={Malcolm Lyon and Jon A. Deakin and John T. Gallagher},
  journal={The Journal of Biological Chemistry},
  year={2002},
  volume={277},
  pages={1040 - 1046}
}
Hepatocyte growth factor/scatter factor, in addition to binding to its specific signal-transducing receptor, Met, also interacts with both heparan and dermatan sulfates with high affinity. We have investigated the comparative role of these two glycosaminoglycans in the activation of Met by hepatocyte growth factor/scatter factor. Using glycosaminoglycan-deficient CHOpgsA-745 cells we have shown that growth factor activity is critically dependent upon glycosaminoglycans, and that heparan sulfate… Expand
The Interactions of Hepatocyte Growth Factor/Scatter Factor and Its NK1 and NK2 Variants with Glycosaminoglycans Using a Modified Gel Mobility Shift Assay
TLDR
It is shown that all three hepatocyte growth factor/scatter factor variants share identical heparan/dermatan sulfate binding properties and that both glycosaminoglycans occupy the same binding site. Expand
Interactions of Hepatocyte Growth Factor/Scatter Factor with Various Glycosaminoglycans Reveal an Important Interplay between the Presence of Iduronate and Sulfate Density*
TLDR
GAG recognition of HGF/SF appears to be primarily driven by electrostatic interactions and exhibits an interesting interplay between requirements for iduronate and sulfate density that may reflect in part a preference for particular sugar chain conformations. Expand
Hepatocyte Growth Factor/Scatter Factor Binds to Small Heparin-derived Oligosaccharides and Stimulates the Proliferation of Human HaCaT Keratinocytes*
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The results suggest that HGF/SF binds to a tetrasaccharide and that although this is sufficient to enable the stimulation of DNA synthesis, longer oligosaccharides are more efficient, perhaps by virtue of their ability to bind more easily other molecules. Expand
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Critical oligosaccharides are identified that promote specific members of the FGF family that are important for wound repair and angiogenesis. Expand
Dermatan Sulfate Binds and Potentiates Activity of Keratinocyte Growth Factor (FGF-7)*
TLDR
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Molecular recognition and modulation of hepatocyte growth factor activity by heparan and dermatan sulfates
Introduction  Hepatocyte growth factor/scatter factor (HGF/SF) is an unusual growth factor in that it binds both heparan sulfate (HS) ( Lyon et al. 1994 ) and dermatan sulfate (DS) ( Lyon et al. 1998Expand
The Binding Properties of Minimal Oligosaccharides Reveal a Common Heparan Sulfate/Dermatan Sulfate-binding Site in Hepatocyte Growth Factor/Scatter Factor That Can Accommodate a Wide Variety of Sulfation Patterns*
TLDR
An unexpected degree of flexibility in the GAG-HGF/SF interface is revealed, allowing a single binding site in the protein to accommodate iduronate-containing sequences of variable sulfation pattern and/or density from different GAGs. Expand
Insights into the structure/function of hepatocyte growth factor/scatter factor from studies with individual domains.
TLDR
The K1, K2 and K4 domains of HGF/SF are sufficient for Met activation, whereas the N and SP domains are not, although the latter domains contribute additional binding sites necessary for receptor activation by full length HGF /SF. Expand
Physiological, Pathophysiological and Therapeutic Roles of Heparin and Heparan Sulfate
Publisher Summary Heparin and heparan sulfate belong to the glycosaminoglycan (GAG) family of carbohydrates. They are linear acidic complex polysaccharides found on the cell surface and in theExpand
The Morphogenic Properties of Oligomeric Endostatin Are Dependent on Cell Surface Heparan Sulfate*
TLDR
It is demonstrated that the effect of oligomeric endostatin can also be inhibited by exogenous glycosaminoglycans in a size-dependent manner, with heparin oligosaccharides containing more than 20 monosACcharide residues having optimal inhibitory activity. Expand
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Hepatocyte Growth Factor/Scatter Factor Binds with High Affinity to Dermatan Sulfate*
We have demonstrated by affinity chromatography that hepatocyte growth factor/scatter factor (HGF/SF) binds strongly to dermatan sulfate (DS), with a similar ionic strength dependence to thatExpand
Differential regulation of hepatocyte growth factor/scatter factor by cell surface proteoglycans and free glycosaminoglycan chains.
TLDR
The 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. Expand
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TLDR
The structural specificity of the HGF-HS interaction is thus shown to be radically different from that previously described for the basic fibroblast growth factor- HS interaction. Expand
Sulfated Oligosaccharides Promote Hepatocyte Growth Factor Association and Govern Its Mitogenic Activity (*)
TLDR
Findings indicate that heparin-like molecules can stabilize HGF oligomers, which may facilitate c-Met receptor dimerization and activation in vitro, as measured by gel filtration and analytical ultracentrifugation. Expand
Heparan Sulfate Oligosaccharides Require 6-O-Sulfation for Promotion of Basic Fibroblast Growth Factor Mitogenic Activity*
TLDR
Analysis of the structure-activity relationships in the dodecasaccharide fractions in particular, suggests that a minimum bFGF activation sequence exists which is dependent on the positioning of at least one 6-O-sulfate group. Expand
Characterization of Heparan Sulfate Oligosaccharides That Bind to Hepatocyte Growth Factor (*)
TLDR
Considering both the substrate specificity and properties of heparitinase I, the above results suggest that the bound octasaccharide should contain two units of IdoA(2SO4)-GlcNSO3(6SO4) contiguously or alternately in the vicinity of the reducing end. Expand
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TLDR
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Hepatocyte growth factor/scatter factor has distinct classes of binding site in heparan sulfate from mammary cells.
Hepatocyte growth factor/scatter factor (HGF/SF) is a heparan sulfate (HS)-binding growth factor and morphogen for mammary epithelial cells that is produced by mammary stromal fibroblasts. HS chains,Expand
Heparin Binding and Oligomerization of Hepatocyte Growth Factor/Scatter Factor Isoforms
TLDR
It is demonstrated that the amino-terminal (N) domain retains the heparin-binding properties of full-length HGF/SF, establishing the importance of the N domain for heparan sulfate glycosaminoglycan and ligand-ligand interactions, and demonstrating a crucial role for HSGAG in receptor binding and signal transduction. Expand
Engineered mutants of HGF/SF with reduced binding to heparan sulphate proteoglycans, decreased clearance and enhanced activity in vivo
TLDR
The results establish the following: the binding sites in HGF/SF for Met and for HSPGs can be dissociated by protein engineering; high-affinity binding of H GF/SF to H SPGs is not essential for signalling; one role of HSPG binding in the HGF /SF system appears to be sequestration and degradation of the growth factor. Expand
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