Characterization of intracellular translocation of Forkheadtranscription factor O (FoxO) members induced by NGF in PC12 cells

Nuclear translocation of Forkhead transcription factors of the O class (FoxOs) is important for the action of growth factors. However it is not known if all members of the FOXO family have the same translocation properties. We examined the effects of nerve growth factor (NGF) on nuclear/cytoplasmic shuttling of FoxO1, FoxO3a and FoxO6 in PC12 cells and determined their translocation kinetics. Our data demonstrated that NGF could induce the nuclear exclusion of FoxO1-GFP and FoxO3a-GFP in PC12 cells with different properties, but had no effect on FoxO6-GFP's nuclear localization and FoxO6-GFP showed an exclusive nuclear localization. Translocation of FoxO1 and FoxO3a could be blocked by K252a and LY294002 but not by PD98059.Moreover, FoxO3a returned to cytoplasm at a higher rate than FoxO1 after NGF stimulation and it was more sensitive than FoxO1 to NGF stimulation.