Synergistic action of R-Ras and IGF-1 on Bcl-xL expression and caspase-3 inhibition in BaF3 cells: R-Ras and IGF-1 control distinct anti-apoptotic kinase pathways.

R-Ras and insulin-like growth factor-1 (IGF-1) synergistically inhibit apoptosis of BaF3 cells upon interleukin-3 deprivation. To characterize the mechanism of this synergistic inhibition, we examined the effect of R-Ras and IGF-1 on several apoptosis-related proteins. Extracellular signal-regulated kinase (ERK) was activated by IGF-1, but not by R-Ras. In contrast, Akt was activated strongly by R-Ras, but weakly by IGF-1. It was also found that R-Ras and IGF-1 cooperatively induced Bcl-xL expression and inhibited caspase-3 activation.