Signalling by HGF/SF and Met: the role of heparan sulphate co-receptors.
The receptor tyrosine kinase Met and its ligand HGF/SF (hepatocyte growth factor/scatter factor) are essential in the signalling pathways required for embryogenesis and tissue regeneration. Aberrant signalling of this complex is also a feature of many tumours and appears to contribute to the growth, invasiveness and metastasis of both carcinomas and sarcomas. HGF/SF, like many other angiogenic growth factors, employs heparan sulphate as co-receptor. The role of this interaction has not been completely defined but appears to be physiologically relevant. Thus the presence of heparin increases the potency of HGF/SF in experiments with cells in culture leading to elevated downstream signalling effects and, although not vital for the Met-HGF/SF interaction, heparin or heparan sulphate is essential for the activity of certain isoforms of HGF/SF, such as NK1 and NK2. Here, we summarize the progress made in understanding the interaction between heparin and heparan sulphate and NK1, NK2 and HGF/SF and we discuss their role in HGF/SF-Met signalling.
Kemp
L E
LE
MRC Centre, Hills Road, Cambridge, UK.
Mulloy
B
B
Gherardi
E
E
D000818:Animals; D002478:Cells, Cultured; D006497:Heparan Sulfate / Q000378:metabolism* / Q000502:physiology; D017228:Hepatocyte Growth Factor / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D006497:Heparan Sulfate; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met