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: Oncoprotein; Protein kinase, tyrosine (receptor); Protein kinase, TK; Membrane protein, integral; Kinase, protein; EC 2.7.10.1; TK group; Met family
Chromosomal Location of Human Ortholog: 7q31
Cellular Component: cell surface; integral to plasma membrane; basal plasma membrane; extracellular region; plasma membrane; integral to membrane
Molecular Function: protein binding; protein-tyrosine kinase activity; protein phosphatase binding; hepatocyte growth factor receptor activity; ATP binding
Biological Process: axon guidance; skeletal muscle development; peptidyl-tyrosine phosphorylation; activation of MAPK activity; protein amino acid autophosphorylation; myoblast proliferation; myotube differentiation; muscle cell migration; hepatocyte growth factor receptor signaling pathway; glucose homeostasis; liver development; signal transduction; cell proliferation; cell surface receptor linked signal transduction; branching morphogenesis of a tube; positive chemotaxis; adult behavior; positive regulation of transcription from RNA polymerase II promoter; brain development; endothelial cell morphogenesis; placenta development
Disease: Hepatocellular Carcinoma; Renal Cell Carcinoma, Papillary, 1
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