BIOMAT Database Logo BIOMAT Database Logo

Hepatocyte growth factor (HGF) stimulates the tyrosine kinase activity of the receptor encoded by the proto-oncogene c-MET. 1991

L Naldini, and E Vigna, and R P Narsimhan, and G Gaudino, and R Zarnegar, and G K Michalopoulos, and P M Comoglio
Department of Biomedical Sciences & Oncology, University of Torino, School of Medicine, Italy.

The human proto-oncogene c-MET encodes a heterodimeric 190 kDa transmembrane protein (p190c-met) with structural features of a tyrosine kinase receptor. The ligand for this putative receptor has not yet been identified. By Northern blot hybridization we found that, among a restricted number of human tissues, c-MET is highly expressed in the liver. This prompted us to test the hypothesis of a functional interaction between the c-MET receptor and Hepatocyte Growth Factor (HGF), a heparin-binding polypeptide consisting of heavy and light chains of 65 and 35 kDa. Nanomolar concentrations of highly purified HGF added to GTL-16 cells, which overexpress the c-MET receptor, enhanced the phosphorylation on tyrosine of the p190c-met kinase. Addition of other known growth factors or serum was ineffective. The kinase activity of the c-MET receptor was also stimulated by HGF in an in vitro assay, after detergent solubilization and partial purification of p190c-met. Moreover, elution of immunoprecipitates obtained with anti-MET antibodies from GTL-16 cell lysates yielded an HGF-responsive kinase activity. These results suggest that HGF, or a growth factor structurally related to HGF, is a candidate ligand for the receptor encoded by c-MET.

UI MeSH Term Description Entries
D007668 Kidney Body organ that filters blood for the secretion of URINE and that regulates ion concentrations. Kidneys
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008168 Lung Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood. Lungs
D010053 Ovary The reproductive organ (GONADS) in female animals. In vertebrates, the ovary contains two functional parts: the OVARIAN FOLLICLE for the production of female germ cells (OOGENESIS); and the endocrine cells (GRANULOSA CELLS; THECA CELLS; and LUTEAL CELLS) for the production of ESTROGENS and PROGESTERONE. Ovaries
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D011505 Protein-Tyrosine Kinases Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors. Tyrosine Protein Kinase,Tyrosine-Specific Protein Kinase,Protein-Tyrosine Kinase,Tyrosine Kinase,Tyrosine Protein Kinases,Tyrosine-Specific Protein Kinases,Tyrosylprotein Kinase,Kinase, Protein-Tyrosine,Kinase, Tyrosine,Kinase, Tyrosine Protein,Kinase, Tyrosine-Specific Protein,Kinase, Tyrosylprotein,Kinases, Protein-Tyrosine,Kinases, Tyrosine Protein,Kinases, Tyrosine-Specific Protein,Protein Kinase, Tyrosine-Specific,Protein Kinases, Tyrosine,Protein Kinases, Tyrosine-Specific,Protein Tyrosine Kinase,Protein Tyrosine Kinases,Tyrosine Specific Protein Kinase,Tyrosine Specific Protein Kinases
D011518 Proto-Oncogene Proteins Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity. Cellular Proto-Oncogene Proteins,c-onc Proteins,Proto Oncogene Proteins, Cellular,Proto-Oncogene Products, Cellular,Cellular Proto Oncogene Proteins,Cellular Proto-Oncogene Products,Proto Oncogene Products, Cellular,Proto Oncogene Proteins,Proto-Oncogene Proteins, Cellular,c onc Proteins
D005260 Female Females
D005753 Gastric Mucosa Lining of the STOMACH, consisting of an inner EPITHELIUM, a middle LAMINA PROPRIA, and an outer MUSCULARIS MUCOSAE. The surface cells produce MUCUS that protects the stomach from attack by digestive acid and enzymes. When the epithelium invaginates into the LAMINA PROPRIA at various region of the stomach (CARDIA; GASTRIC FUNDUS; and PYLORUS), different tubular gastric glands are formed. These glands consist of cells that secrete mucus, enzymes, HYDROCHLORIC ACID, or hormones. Cardiac Glands,Gastric Glands,Pyloric Glands,Cardiac Gland,Gastric Gland,Gastric Mucosas,Gland, Cardiac,Gland, Gastric,Gland, Pyloric,Glands, Cardiac,Glands, Gastric,Glands, Pyloric,Mucosa, Gastric,Mucosas, Gastric,Pyloric Gland
D005786 Gene Expression Regulation Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation. Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression

Related Publications

L Naldini, and E Vigna, and R P Narsimhan, and G Gaudino, and R Zarnegar, and G K Michalopoulos, and P M Comoglio
Defective posttranslational processing activates the tyrosine kinase encoded by the MET proto-oncogene (hepatocyte growth factor receptor).
December 1991, Molecular and cellular biology,
L Naldini, and E Vigna, and R P Narsimhan, and G Gaudino, and R Zarnegar, and G K Michalopoulos, and P M Comoglio
Tyrosines1234-1235 are critical for activation of the tyrosine kinase encoded by the MET proto-oncogene (HGF receptor).
January 1994, Oncogene,
L Naldini, and E Vigna, and R P Narsimhan, and G Gaudino, and R Zarnegar, and G K Michalopoulos, and P M Comoglio
Hepatocyte growth factor/scatter factor and its receptor, the c-met proto-oncogene product.
December 1993, Biochimica et biophysica acta,
L Naldini, and E Vigna, and R P Narsimhan, and G Gaudino, and R Zarnegar, and G K Michalopoulos, and P M Comoglio
[Coexpression of hepatocyte growth factor-scatter factor (HGF-SF) and HGF-SF receptors (c-met proto-oncogene) in mammalian brain].
January 1994, Verhandlungen der Deutschen Gesellschaft fur Pathologie,
L Naldini, and E Vigna, and R P Narsimhan, and G Gaudino, and R Zarnegar, and G K Michalopoulos, and P M Comoglio
Identification of the hepatocyte growth factor receptor as the c-met proto-oncogene product.
February 1991, Science (New York, N.Y.),
L Naldini, and E Vigna, and R P Narsimhan, and G Gaudino, and R Zarnegar, and G K Michalopoulos, and P M Comoglio
Hepatocyte growth factor receptor and the c-met oncogene.
October 1991, Hepatology (Baltimore, Md.),
L Naldini, and E Vigna, and R P Narsimhan, and G Gaudino, and R Zarnegar, and G K Michalopoulos, and P M Comoglio
Expression of hepatocyte growth factor and its receptor c-met proto-oncogene in hepatocellular carcinoma.
April 1997, Hepatology (Baltimore, Md.),
L Naldini, and E Vigna, and R P Narsimhan, and G Gaudino, and R Zarnegar, and G K Michalopoulos, and P M Comoglio
Structural and functional characterization of the mouse c-met proto-oncogene (hepatocyte growth factor receptor) promoter.
February 1998, Biochimica et biophysica acta,
L Naldini, and E Vigna, and R P Narsimhan, and G Gaudino, and R Zarnegar, and G K Michalopoulos, and P M Comoglio
Expression of hepatocyte growth factor and its receptor, the c-met proto-oncogene, in hepatocellular carcinoma.
March 1997, Hepatology (Baltimore, Md.),
L Naldini, and E Vigna, and R P Narsimhan, and G Gaudino, and R Zarnegar, and G K Michalopoulos, and P M Comoglio
Hepatocyte growth factor-scatter factor (HGF-SF) and the c-met receptor. Introduction.
January 1993, EXS,
Copied contents to your clipboard!