MEK/ERK pathway mediates insulin-promoted degradation of MKP-3 protein in liver cells

► In this study, we examined the mechanism of insulin promoted MKP-3 protein degradation in cultured liver cells. ► We demonstrated that the MEK/ERK pathway mediates the effect of insulin on degrading MKP-3 protein. ► We further confirmed that ERK phosphorylation deficient MKP-3 mutant is resistant to insulin promoted protein degradation. ► We also showed that the MEK/ERK pathway affects glucose output, possibly through regulating MKP-3 protein level.