Cross-talk between the proto-oncogenes Met and Ron
作者： A Follenzi , S Bakovic , P Gual , M C Stella , P Longati
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摘要: Scatter Factors control a complex genetic program known as ‘invasive growth’. HGF (Scatter factor 1) and MSP Factor 2) bind to tyrosine kinase receptors encoded by the proto-oncogenes MET RON. Using appropriate ‘kinase inactive’ mutant receptors, we show that ligand-induced activation of Met results in transphosphorylation Ron, vice versa. Transphosphorylation is direct, it occurs or Ron lacking docking sites for signal transducers. Phosphate groups are transferred phosphorylation responsible both up-regulation (Met: Y1234/Y1235 Ron: Y1238/Y1239) generation transducer Y1349/Y1356 Y1353/Y1360). The specifically takes place receptor subfamily, not observed between ErbB1, ErbB2 TrkA. Cross-linking experiments non-covalent Met-Ron complexes present on cell surface, before dimerization. Co-expression inactive with naturally-occurring oncogenic mutants suppresses transforming phenotype, suggesting dominant negative role inefficient partner. These data that, while specific their ligands, scatter cross-talk cooperate intracellular signaling.
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