Hepatocyte growth factor/scatter factor and its interaction with heparan sulphate and dermatan sulphate

2003 ◽  
Vol 31 (2) ◽  
pp. 352-353 ◽  
Author(s):  
K. Catlow ◽  
J.A. Deakin ◽  
M. Delehedde ◽  
D.G. Fernig ◽  
J.T. Gallagher ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Map Kinase ◽  
Heparan Sulphate ◽  
Dermatan Sulphate ◽  
Scatter Factor ◽  
Activation Assay ◽  
Map Kinase Pathway ◽  
Hepatocyte Growth ◽  
Kinase Pathway

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.

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

1999 ◽  
Vol 112 (12) ◽  
pp. 1999-2009 ◽  
Author(s):  
J.A. Deakin ◽  
M. Lyon
Keyword(s):  
Growth Factor ◽  
Cell Surface ◽  
Hepatocyte Growth Factor ◽  
Cell Motility ◽  
Heparan Sulphate ◽  
Mitogen Activated Protein Kinase ◽  
Dermatan Sulphate ◽  
Mitogen Activated Protein ◽  
Hepatocyte Growth ◽  
Darby Canine Kidney

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.

scholarly journals Activation of Both MAP Kinase and Phosphatidylinositide 3-Kinase by Ras Is Required for Hepatocyte Growth Factor/Scatter Factor–induced Adherens Junction Disassembly

1998 ◽  
Vol 9 (8) ◽  
pp. 2185-2200 ◽  
Author(s):  
Sandra Potempa ◽  
Anne J. Ridley
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Map Kinase ◽  
Adherens Junctions ◽  
Adherens Junction ◽  
Dominant Negative ◽  
Cell Junctions ◽  
Scatter Factor ◽  
Cell Scattering ◽  
Hepatocyte Growth

Hepatocyte growth factor/scatter factor (HGF/SF) stimulates the motility of epithelial cells, initially inducing centrifugal spreading of colonies followed by disruption of cell–cell junctions and subsequent cell scattering. In Madin–Darby canine kidney cells, HGF/SF-induced motility involves actin reorganization mediated by Ras, but whether Ras and downstream signals regulate the breakdown of intercellular adhesions has not been established. Both HGF/SF and V12Ras induced the loss of the adherens junction proteins E-cadherin and β-catenin from intercellular junctions during cell spreading, and the HGF/SF response was blocked by dominant-negative N17Ras. Desmosomes and tight junctions were regulated separately from adherens junctions, because they were not disrupted by V12Ras. MAP kinase, phosphatidylinositide 3-kinase (PI 3-kinase), and Rac were required downstream of Ras, because loss of adherens junctions was blocked by the inhibitors PD098059 and LY294002 or by dominant-inhibitory mutants of MAP kinase kinase 1 or Rac1. All of these inhibitors also prevented HGF/SF-induced cell scattering. Interestingly, activated Raf or the activated p110α subunit of PI 3-kinase alone did not induce disruption of adherens junctions. These results indicate that activation of both MAP kinase and PI 3-kinase by Ras is required for adherens junction disassembly and that this is essential for the motile response to HGF/SF.

scholarly journals Characterization of the Scatter Factor/Hepatocyte Growth Factor Gene Promoter

1995 ◽  
Vol 270 (2) ◽  
pp. 830-836 ◽  
Author(s):  
Antje Plaschke-Schlütter ◽  
Jürgen Behrens ◽  
Ermanno Gherardi ◽  
Walter Birchmeier
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Gene Promoter ◽  
Scatter Factor ◽  
Factor Gene ◽  
Growth Factor Gene ◽  
Hepatocyte Growth

scholarly journals Paracrine Regulation of Germinal Center B Cell Adhesion through the c-Met–Hepatocyte Growth Factor/Scatter Factor Pathway

1997 ◽  
Vol 185 (12) ◽  
pp. 2121-2131 ◽  
Author(s):  
Robbert van der Voort ◽  
Taher E.I. Taher ◽  
Robert M.J. Keehnen ◽  
Lia Smit ◽  
Martijn Groenink ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
T Cell ◽  
B Cells ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Tyrosine Kinase ◽  
B Cell ◽  
Germinal Center ◽  
Scatter Factor ◽  
Hepatocyte Growth

T cell–dependent humoral immune responses are initiated by the activation of naive B cells in the T cell areas of the secondary lymphoid tissues. This primary B cell activation leads to migration of germinal center (GC) cell precursors into B cell follicles where they engage follicular dendritic cells (FDC) and T cells, and differentiate into memory B cells or plasma cells. Both B cell migration and interaction with FDC critically depend on integrin-mediated adhesion. To date, the physiological regulators of this adhesion were unkown. In the present report, we have identified the c-met–encoded receptor tyrosine kinase and its ligand, the growth and motility factor hepatocyte growth factor/scatter factor (HGF/SF), as a novel paracrine signaling pathway regulating B cell adhesion. We observed that c-Met is predominantly expressed on CD38+CD77+ tonsillar B cells localized in the dark zone of the GC (centroblasts). On tonsil B cells, ligation of CD40 by CD40-ligand, induces a transient strong upregulation of expression of the c-Met tyrosine kinase. Stimulation of c-Met with HGF/SF leads to receptor phosphorylation and, in addition, to enhanced integrin-mediated adhesion of B cells to both VCAM-1 and fibronectin. Importantly, the c-Met ligand HGF/SF is produced at high levels by tonsillar stromal cells thus providing signals for the regulation of adhesion and migration within the lymphoid microenvironment.

scholarly journals Normal and Malignant Prostate Epithelial Cells Differ in Their Response to Hepatocyte Growth Factor/Scatter Factor

2001 ◽  
Vol 159 (2) ◽  
pp. 579-590 ◽  
Author(s):  
Glenn A. Gmyrek ◽  
Marc Walburg ◽  
Craig P. Webb ◽  
Hsiao-Man Yu ◽  
Xueke You ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Hepatocyte Growth Factor ◽  
Scatter Factor ◽  
Prostate Epithelial Cells ◽  
Hepatocyte Growth ◽  
Malignant Prostate

Hepatocyte Growth Factor/Scatter Factor Stimulates Hair Growth of Mouse Vibrissae in Organ Culture

1994 ◽  
Vol 103 (3) ◽  
pp. 306-309 ◽  
Author(s):  
Toshimasa Jindo ◽  
Ryoji Tsuboi ◽  
Ryusuke Imai ◽  
Kenji Takamori ◽  
Jeffrey S Rubin ◽  
...  
Keyword(s):  
Growth Factor ◽  
Organ Culture ◽  
Hepatocyte Growth Factor ◽  
Hair Growth ◽  
Scatter Factor ◽  
Hepatocyte Growth
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