Met: a proto-oncogenic receptor tyrosine kinase with high affinity for hepatocyte growth factor. The primary single chain precursor protein is post-translationally cleaved to produce the 45 kDa alpha- and 145 kDa beta-subunits, which are disulfide linked to form the mature receptor. Ligand-binding induces autophosphorylation at multiple tyrosines, which recruit several downstream signaling components, including Gab1, c-Cbl and PI3 kinase. Activating point mutations cause hereditary papillary renal carcinoma. Mutations also seen in sporadic renal cell carcinoma and childhood hepatocellular carcinoma. Upregulation in carcinomas and sarcomas correlates with metastasis and poor outcome. Some gastric carcinomas harbor a translocation that creates an activated TPR-Met fusion protein. A small molecule inhibitor (PHA-665752) shows an effect in gastric carcinoma xenografts. Inhibitors: SU11274, PHA-665752, mAbs. Two alternatively spliced human isoforms have been reported.
Protein type: EC 2.7.10.1; Kinase, protein; Membrane protein, integral; Met family; Oncoprotein; Protein kinase, TK; Protein kinase, tyrosine (receptor); TK group
Chromosomal Location of Human Ortholog: 7q31
Cellular Component: basal plasma membrane; cell surface; integral to plasma membrane; plasma membrane
Molecular Function: hepatocyte growth factor receptor activity; protein binding; protein phosphatase binding; protein-tyrosine kinase activity
Biological Process: branching morphogenesis of a tube; cell proliferation; endothelial cell morphogenesis; positive chemotaxis; positive regulation of transcription from RNA polymerase II promoter; signal transduction
Disease: Deafness, Autosomal Recessive 97; Hepatocellular Carcinoma; Osteofibrous Dysplasia, Susceptibility To; Renal Cell Carcinoma, Papillary, 1
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