The alpha-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 alpha-isoform of glycogen synthase kinase-3 (GSK3 alpha) 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 GSK3 alpha activity towards glycogen synthase, inhibitor-2 and c-jun. The specificity of GSK3 alpha was similar to GSK3 beta, but with the synthetic peptide substrate heparin stimulated the dephosphorylated form of GSK3 alpha (6-fold) more than GSK3 beta (1.8-fold). After phosphorylation, both isoforms were stimulated 15-20-fold by heparin.
Sutherland
C
C
Department of Biochemistry, University of Dundee, Scotland, UK.
Cohen
P
P
D000595:Amino Acid Sequence; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors*; D038362:Glycogen Synthase Kinase 3; D038341:Glycogen Synthase Kinases; D066298:In Vitro Techniques; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors*; D008969:Molecular Sequence Data; D009132:Muscles / Q000201:enzymology*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011817:Rabbits; D019893:Ribosomal Protein S6 Kinases; D038744:Ribosomal Protein S6 Kinases, 90-kDa
D008869:Microtubule-Associated Proteins; D038341:Glycogen Synthase Kinases; D017346:Protein Serine-Threonine Kinases; D019893:Ribosomal Protein S6 Kinases; D038744:Ribosomal Protein S6 Kinases, 90-kDa; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3