인슐린 세포사멸 억제활성과 FAK/p130 Cas 신호전달과의 관계 = Antiapoptotic activity of insulin and FAK/p130Cas signaling pathway

다국어 초록 (Multilingual Abstract)

The focal adhesion kinase (pp125FAK) is a nonreceptor tyrosine kinase involved in integrin-mediated signal transduction pathway which includes the activation of' the Ras/mitogen-activated protein (MAP) kinase cascade. Tyrosine phosphorylation of FAK is essential to its activity, as interference with FAK phosphorylation results in apoptotic death in various cellular systems. Insulin receptor has the ability to suppress apoptotic death mediated by growth factor withrawal using signal pathways which is dependent on protein farnesylation. In the present study, we investigated the impact of FAK tyrosine phosphorylation in two responses of insulin: (1) Ras/MAP kinase activation, and (2) Prevention of apoptosis. To this purpose, we examined whethei@ insulin can mudulate FAK activity together with p130Cas, which is a downstream component of FAK signaling. It was also investigated whether insulin can protect cells from apoptosis in CHO IR/△SOS cells. lacking the intrinsic function of mSOS1-Ras activation. Unexpectedly, insulin decreased the degree of tyrosine phosphorylation of FAK as well as pl30Cas where it protected cells from apoptosis both in wild (CHO-IR) and mSOS-Ras-deficient (CHO-IR/△SOS) cells. These results suggest that neither the Ras activity nor FAK activity play role in antlapoptotic protection by insulin. We also tested the ability of other survival factor (DPI) or death factor (TNF-α) to affect insulin's function to dephosphorylate p130Cas or to protect cells from apoptosis. Neither of them could affect tyrosine phosphorylation of p130Cas without regards to their antiapoptotic- and proapoptotic activities, respectively. Taken together, it is suggested that FAK/p130Cas signaling does not play any significant role(s) in insulin's antiapoptotic protection.