Kinase Activity in Invasive Tumors

The ability of oncogenic Met to facilitate chemically induced transformation of a human osteogenic sarcoma cell line led to the discovery of the MET proto-oncogene. Met, the gene's normal product, is an unique receptor tyrosine kinase that can be separated from most others by its biosynthesis and structural characteristics. This transmembrane protein is made up of a single-chain precursor that is cleaved at a basic amino acid position by intracellular proteolysis, resulting in a disulfide-linked heterodimer. It has a multipurpose docking site in its C-terminal intracellular region that interacts to numerous signaling molecules. These characteristics identify the Met receptor tyrosine kinase family, which includes Met, Ron, and c-Sea, the latter of which may be the chicken ortholog of Ron. HGF, also known as scatter factor, is the Met receptor's ligand. HGF was shown to be a mitogenic factor for liver cells as well as a scattering/motility factor for epithelial cells produced from fibroblasts.

Author(s): David Richards

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