The Molecular basis of tyrosine kinase signaling

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To elucidate the molecular basis for the regulatory mechanisms of Src-mediated tumor progression, we analyzed the function of a transmembrane raft adaptor Cbp (Csk binding protein), and a novel membrane adaptor p18 which was identified from lipid rafts of late endosomes. We found that Cbp expression is downregulated via some oncogenic pathways, and that Cbp suppresses Src function by sequestering activated Src to lipid rafts. These findings suggest that Cbp functions as a type of tumor suppressor. We also found that p18 plays a crucial role in regulating endosome dynamics as well as cell growth by recruiting Src/Ras-MEK1-ERK pathway to late endosomes. These results indicate that the p18 pathway is crucial for regulating cell transformation and tumor growth.