Structure of the met protein and variation of met protein kinase activity among human tumour cell lines.
An in vitro autophosphorylation assay has been used to demonstrate that there is considerable variation in met associated protein kinase among human tumour cell lines. Of particular note was the very high level of autophosphorylation of the 140 kD met protein (p140met) in experiments with A431 human cervical carcinoma cells. In contrast in experiments with Daoy human medulloblastoma cells we failed to detect phosphorylation of p140met; instead a high level of phosphorylation of a 132 kD protein was observed. To help understand the basis for the variation in kinase activity and to learn more about the structure of the mature met protein we have analysed p140met in SDS-polyacrylamide gels under non-reducing conditions. Under these conditions the met protein had an apparent molecular weight of 165,000 indicating that the mature met protein may exist as an alpha beta complex in which p140met (designated the beta subunit) is joined by disulphide bonds to a smaller, 25 kD, alpha-chain. We have identified a potential proteolytic cleavage site with the sequence Lys-Arg-Lys-Lys-Arg-Ser at amino acids 303-308 in the human met protein that may account for cleavage of the met protein into alpha and beta subunits.
D000595:Amino Acid Sequence; D000937:Antigen-Antibody Reactions; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D008970:Molecular Weight; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000201:enzymology*
D011518:Proto-Oncogene Proteins; D011494:Protein Kinases; D066246:ErbB Receptors