Mitogen inactivation of glycogen synthase kinase-3 beta in intact cells via serine 9 phosphorylation

• Published in: Biochemical journal Vol. 303 ( Pt 3); no. 3; pp. 701 - 704
• Main Authors: Stambolic, V, Woodgett, J R
• Format: Journal Article
• Language: English
• Published: England 01.11.1994
• Subjects: Amino Acid Sequence; Calcium-Calmodulin-Dependent Protein Kinases - antagonists & inhibitors; Calcium-Calmodulin-Dependent Protein Kinases - genetics; Calcium-Calmodulin-Dependent Protein Kinases - metabolism; Glycogen Synthase Kinase 3; Glycogen Synthase Kinases; HeLa Cells; Humans; Mitogens - pharmacology; Molecular Sequence Data; Phosphorylation; Point Mutation; Serine - metabolism
• ISSN: 0264-6021; 1470-8728
• DOI: 10.1042/bj3030701

Glycogen synthase kinase-3 (GSK-3), a protein-serine kinase implicated in cell-fate determination and differentiation, phosphorylates several regulatory proteins that are activated by dephosphorylation in response to hormones or growth factors. GSK-3 beta is phosphorylated in vitro at serine 9 by p70 S6 kinase and p90rsk-1, resulting in its inhibition [Sutherland, Leighton, and Cohen (1993) Biochem. J. 296, 15-19]. Using HeLa cells expressing GSK-3 beta or a mutant containing alanine at residue 9, we demonstrate that serine 9 is modified in intact cells and is targeted specifically by p90rsk-1, and that phosphorylation leads to loss of activity. Since p90rsk-1 is directly activated by mitogen-activated protein kinases, agonists of this pathway, such as insulin, repress GSK-3 function.