Molecular characteristics of HGF and the gene, and its biochemical aspects.
Hepatocyte growth factor (HGF) was initially identified as a potent mitogen for mature hepatocytes in sera of partially hepatectomized rats and seems to be the long sought after hepatotrophic factor for liver regeneration. HGF, first purified to homogeneity from rat platelets in 1986, is a disulfide-linked heterodimer molecule composed of a 69 kDa alpha-subunit and a 34 kDa beta-subunit. In 1989, cDNAs of both human and rat HGF were cloned and the primary structure of HGF was determined. This factor is derived from a single chain precursor of 728 amino acid residues, which is proteolytically processed to form mature HGF. While HGF has no homology wit any known growth factors, it does have a considerable homology (38%) with plasminogen. The alpha-subunit of HGF contains four kringle domains and the beta-subunit resembles serine proteases, but there is no evidence of protease activity. The human HGF-encoding gene is composed of 18 exons and 17 introns, spans about 70 kb and located on chromosome 7q11.1-21 in humans. The overall gene organization of the HGF gene is highly homologous with that of plasminogen. These genes seem to be derived from a common ancestor, by gene duplication. Artificially mutated HGFs with deletion of the N-terminal hairpin structure or the first or second kringle domain lose almost completely all biological activities, hence these domains are probably essential for the biological activities of HGF and possibly for binding to its receptor. A high affinity receptor for HGF with a Kd value of 20-30 pM was detected on various epithelial cells, including hepatocytes. The c-met proto-oncogene product was recently identified to be an HGF receptor. Transfection of c-met cDNA into COS cells provided further evidence that the c-met product is a functional high-affinity receptor for HGF capable of transducing the mitogenic signal of HGF.
Mizuno
K
K
Department of Biology, Faculty of Science, Kyushu University, Fukuoka, Japan.
Nakamura
T
T
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002897:Chromosomes, Human, Pair 7; D005091:Exons; D014644:Genetic Variation; D017228:Hepatocyte Growth Factor / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D007438:Introns; D008115:Liver Regeneration; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D000090063:Proto-Oncogene Mas; D051381:Rats; D017386:Sequence Homology, Amino Acid
C000715470:MAS1 protein, human; D046911:Macromolecular Substances; D000090063:Proto-Oncogene Mas; D017228:Hepatocyte Growth Factor