The hepatocyte growth factor and its receptor.
Hepatocyte growth factor/scatter factor (HGF/SF) is secreted by cells of mesodermal origin and shows powerful mitogenic, motogenic and morphogenic activities on epithelial and endothelial cells. It is a heparin-binding polypeptide with an alpha/beta heterodimeric structure, showing structural homologies with enzymes of the blood clotting cascade. HGF binds with high affinity to the receptor encoded by the MET protooncogene (p190MET). The MET receptor is a heterodimer of two disulfide-linked subunits (alpha and beta); the alpha subunit is extracellular, while the beta is transmembrane and endowed with tyrosine kinase activity. The HGF-triggered signalling is mediated by different cytoplasmic effectors, including phosphatidylinositol 3-kinase, phospholipase C-gamma, and Src-related tyrosine kinases. p190MET is expressed in several normal epithelial tissues (e.g., liver, gastrointestinal tract, kidney) and is often overexpressed in neoplastic cells. p190MET expression has been reported also in central nervous system microglia, a monocyte-derived cell population. We recently found that p190MET is expressed in selected peripheral blood cell populations, such as macrophages. The amount of both mRNA and protein is barely detectable, while it is dramatically increased upon activation. These findings suggest that HGF may play a role in hemopoietic cell signaling, during activation and differentiation of blood cell lineages.
Galimi
F
F
Department of Biomedical Sciences and Oncology, University of Turin, School of Medicine, Italy.
Brizzi
M F
MF
Comoglio
P M
PM
D000818:Animals; D002277:Carcinoma / Q000378:metabolism; D002455:Cell Division; D002465:Cell Movement; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D005786:Gene Expression Regulation; D005796:Genes; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008938:Mitosis; D009000:Monocytes / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism; D009928:Organ Specificity; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D019859:Proto-Oncogene Proteins c-met; D011519:Proto-Oncogenes; D011817:Rabbits; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction
D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D017228:Hepatocyte Growth Factor; D011505:Protein-Tyrosine Kinases; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases