Phosphorylation and inactivation of glycogen synthase kinase 3 by protein kinase A

Xianjun Fang, Shuang Xing Yu, Yiling Lu, Robert C. Bast, James R. Woodgett, Gordon B. Mills

    Research output: Contribution to journalArticlepeer-review

    553 Scopus citations

    Abstract

    Glycogen synthase kinase 3 (GSK-3) is implicated in multiple biological processes including metabolism, gene expression, cell fate determination, proliferation, and survival. GSK-3 activity is inhibited through phosphorylation of serine 21 in GSK-3α and serine 9 in GSK-3β. These serine residues of GSK-3 have been previously identified as targets of protein kinase B (PKB/Akt), a serine/threonine kinase located downstream of phosphatidyl-inositol 3-kinase. Here, we show that serine 21 in GSK-3α and serine 9 in GSK-3β are also physiological substrates of cAMP-dependent protein kinase A. Protein kinase A physically associates with, phosphorylates, and inactivates both isoforms of GSK-3. The results indicate that depending on the stimulatory context, the activity of GSK-3 can be modulated either by growth factors that work through the phosphatidylinositol 3-kinase-protein kinase B cascade or by hormonal stimulation of G protein-coupled receptors that link to changes in intracellular cAMP levels.

    Original languageEnglish (US)
    Pages (from-to)11960-11965
    Number of pages6
    JournalProceedings of the National Academy of Sciences of the United States of America
    Volume97
    Issue number22
    DOIs
    StatePublished - Oct 24 2000

    ASJC Scopus subject areas

    • General

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