The α-isoform of glycogen synthase kinase-3 from rabbit skeletal muscle is inactivated by p70 S6 kinase or MAP kinase-activated protein kinase-1 in vitro

The α-isoform of glycogen synthase kinase-3 (GSK3α) was inactivated by 80% towards a synthetic peptide substrate upon incubation with Mg-ATP and either MAP kinase-activated protein (MAPKAP) kinase-1 or p70 S6 kinase. Inactivation by either kinase resulted from the phosphorylation of Ser-21 and was reversed by treatment with protein phosphatase 2A₁. Phosphorylation also decreased GSK3α activity towards glycogen synthase, inhibitor-2 and c-jun. The specificity of GSK3a was similar to GSK3β, but with the synthetic peptide substrate heparin stimulated the dephosphorylated form of GSK3α (6-fold) more than GSK3β(1.8-fold). After phosphorylation, both isoforms were stimulated 15-20-fold by heparin.