Studies Of The Functions Of The Transmembrane Adapter Protein Cbp In Receptor Tyrosine Kinases Related Signal Transduction And Cell Activities

Stimulation of mammalian cells with growth factors results in cell growth, differentiation,migration and/or other changes. Growth factors cannot penetrate the cell membrane by themselves,and they transduce signals into the cell through binding transmembrane tyrosine kinases (receptortyrosine kinases) and changing the kinase activities of the receptors. The nonreceptor tyrosinekinase Src is required for activating some of the subsequent signal transduction pathways byreceptor tyrosine kinases. Src and its related family members is mainly associated withmembranes, while Csk (one of the major negative regulators of Src) is mainly localized in cytosol.People had wondered how Csk regulated Src kinase. In 2000, the scientists firstly reported that thetransmembrane protein Cbp (Csk protein ) could recruit Csk from cytosol to membrane, andoverexpression of Cbp results in down-regulation of Src kinase activity(Kawabuchi et al., 2000;Tomas Brdicka et al., 2000). Moreover, the scientist proved that the interaction of Cbp and Cskwas essential for maintaining the low kinase activity state of Src family kinase in quiescent Tcells(Tomas Brdicka et al., 2000). Therefore we hypothesized that Cbp may also regulate growthfactor activated signal transduction through Csk and Src. The biochemical studies indicated thatCbp could suppress EGF (epidermal growth factor) induced Src, MAPK(mitogen-activatedprotein kinase)and PKB/Akt(protein kinase B/Akt)activation. However, most of theseexperimental results was reported by other scientists ahead of us(Matsuoka et al., 2004). So wedeepen the study by additional cell biology experiments. Our results showed that Cbp suppressedEGF-induced transformation of fibroblast cells into tumor-like cells and also suppressed thegrowth of tumor cells in soft agar. In conclusion, the major contribution of this work was the firstdemonstration of some evidence that support Cbp to be a negative regulator of tumor initiationand growth. Besides, we also made some primary discoveries in the regulation of FGFR(fibroblast growth factor receptor) functions by Cbp and other research areas.