Dysregulation of Met receptor tyrosine kinase activity in invasive tumors

The MET protooncogene was discovered because of the ability of oncogenic Met to mediate chemically induced transformation of a human osteogenic sarcoma cell line (1). The normal product of this gene, Met, is an unusual receptor tyrosine kinase that can be distinguished from most other such proteins on the basis of its biosynthesis and its structural features. This transmembrane protein is synthesized as a single-chain precursor, which undergoes intracellular proteolytic cleavage at a basic amino acid site, yielding a disulfide-linked heterodimer. Its C-terminal, intracellular region contains a multifunctional docking site that binds to various signaling molecules. These features define a Met receptor tyrosine kinase family consisting of three related proteins, Met, Ron, and c-Sea, the last of which may be the chicken ortholog of Ron.