Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B

Darren A. E. Cross, Dario R. Alessi, Philip Cohen, Mirjana Andjelkovich, Brian A. Hemmings

    Research output: Contribution to journalLetterpeer-review

    4473 Citations (Scopus)


    GLYCOGEN synthase kinase-3 (GSK3)1 is implicated in the regulation of several physiological processes, including the control of glycogen2 and protein3 synthesis by insulin, modulation of the transcription factors AP-1 and CREB4–6, the specification of cell fate in Drosophila 7 and dorsoventral patterning in Xenopus embryos8. GSK3 is inhibited by serine phosphorylation in response to insulin or growth factors3,9–11 and in vitro by either MAP kinase-activated protein (MAPKAP) kinase-1 (also known as p90rsk) or p70 ribosomal S6 kinase (p70S6k)12,13. Here we show, however, that agents which prevent the activation of both MAPKAP kinase-1 and p70S6k by insulin in vivo do not block the phosphorylation and inhibition of GSK3. Another insulin-stimulated protein kinase inactivates GSK3 under these conditions, and we demonstrate that it is the product of the proto-oncogene protein kinase B (PKB, also known as Akt/RAC). Like the inhibition of GSK3 (refs 10, 14), the activation of PKB is prevented by inhibitors of phosphatidylinositol (PI) 3-kinase.
    Original languageEnglish
    Pages (from-to)785-789
    Number of pages5
    Publication statusPublished - 28 Dec 1995


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