(A) Upon entering the cell, cortisol binds to GR and leads to receptor dimerization. For gaining full activity, GR is phosphorylated at Ser211 to activate the transcription of target genes such as IGFBP1, GILZ and SDPR. Phosphorylation of Ser211 is mediated, at least in part, by a mechanism involving active GSK-3. PP1α dephosphorylates and activates GSK-3. (B) Knockdown of PP1α prevents GSK-3 activation, and inhibition as well as knockdown of GSK-3 diminishes GR-Ser211 phosphorylation, its activation and stimulation of target gene transcription.