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

V Stambolic, JR Woodgett - Biochemical Journal, 1994 - portlandpress.com
V Stambolic, JR Woodgett
Biochemical Journal, 1994portlandpress.com
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 …
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.
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