Isoforms of human HGF and their biological activities.
Hepatocyte growth factor (HGF) is a plasminogen-like protein thought to be a humoral mediator of liver regeneration. It is produced by stromal fibroblasts and acts as a mitogen for a variety of target cells. Scatter factor, a stimulant of epithelial and vascular endothelial cell motility, is the same as HGF. HGF mediates its effects by activation of a membrane-spanning tyrosine kinase, recently identified as the met proto-oncogene product. We purified a naturally occurring hepatocyte growth factor variant, whose predicted sequence extends only through the second kringle domain of this plasminogen-related molecule. This smaller molecule, derived from an alternative HGF transcript, lacked mitogenic activity but specifically inhibited HGF-induced mitogenesis. Cross-linking studies demonstrated that the truncated molecule competes with HGF for binding to the c-met proto-oncogene product. Thus, the same gene encodes both a growth factor and its direct antagonist.
Chan
A
A
Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, MD 20892.
Rubin
J
J
Bottaro
D
D
Hirschfield
D
D
Chedid
M
M
Aaronson
S A
SA
D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005091:Exons; D014644:Genetic Variation; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007438:Introns; D008969:Molecular Sequence Data; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D019859:Proto-Oncogene Proteins c-met; D011519:Proto-Oncogenes; D011956:Receptors, Cell Surface / Q000502:physiology*; D015398:Signal Transduction
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D017228:Hepatocyte Growth Factor; D004247:DNA; D011505:Protein-Tyrosine Kinases; D019859:Proto-Oncogene Proteins c-met