GRK2-Deficiency Reduces Insulin Activation of ERK1/2 and Mitogenesis in Mouse Liver FL83B Cells

We have reported that G protein coupled receptor kinase-2 (GRK2) negatively regulates insulin receptor signaling leading to glycogen synthesis in mouse liver derived FL83B cells. Since insulin is a potent cellular growth hormone, present study investigated the effect of GRK2 on insulin-stimulated MAP kinase pathway leading to mitogenesis. Specific GRK2 siRNA was used to knock-down (>90%) GRK2 in FL83B cells. Effect of insulin on ERK1/2 activation and [ 3 H]-methyl thymidine incorporation were determined in GRK2 siRNA-treated and control cells. Insulinstimulated ERK1/2 activation was attenuated in GRK2-deficient as compared to control cells. Basal and insulinstimulated [ 3 H]-methyl thymidine incorporation, a measure of mitogenesis, was lower in GRK2-deficient cells. The data suggest that GRK2 may have positive regulatory role in insulin-stimulated MAP kinase pathway and mitogenesis. The present study together with our earlier report on insulin-induced glycogen synthesis indicates a dual role of GRK2 in insulin receptor signaling/function.