Heparin modulates the receptor-binding and mitogenic activity of hepatocyte growth factor on hepatocytes.
Hepatocyte growth factor (HGF) is a mitogen for hepatocytes, having high affinity for heparin. In this study, we examined the function of cell surface heparin-like molecules in HGF/receptor interaction and HGF-induced mitogenic activity using hepatocytes. Binding studies using 125I-HGF showed that more than 85% of bound HGF was released from the cell surface by washing with heparin. This procedure also released HGF from the c-Met protein, which is a component of the high-affinity receptor. In addition, heparitinase digestion of hepatocytes reduced the HGF bound to c-Met protein. Furthermore, excess heparin added during the binding of 125I-HGF to hepatocytes, significantly diminished HGF bound to c-Met protein. Moreover, when DNA synthesis of hepatocytes was repressed and retarded by excess HGF, exogenous heparin restored it. These results suggest that HGF is bound to c-Met protein and that its mitogenic activity is regulated by heparin-like molecules on hepatocytes.
Naka
D
D
Biosciences Laboratory, Mitsubishi Kasei Corporation Research Center, Yokohama, Japan.
Ishii
T
T
Shimomura
T
T
Hishida
T
T
Hara
H
H
D000818:Animals; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D006493:Heparin / Q000378:metabolism* / Q000494:pharmacology; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008934:Mitogens; D011133:Polysaccharide-Lyases / Q000494:pharmacology; D019859:Proto-Oncogene Proteins c-met; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism
D008934:Mitogens; D011994:Recombinant Proteins; D017228:Hepatocyte Growth Factor; D006493:Heparin; D004247:DNA; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases; D011133:Polysaccharide-Lyases; C021349:heparitinsulfate lyase