Blog
About

  • Record: found
  • Abstract: found
  • Article: found
Is Open Access

What Are the bona fide GSK3 Substrates?

*

International Journal of Alzheimer's Disease

SAGE-Hindawi Access to Research

Read this article at

Bookmark
      There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

      Abstract

      Nearly 100 proteins are proposed to be substrates for GSK3, suggesting that this enzyme is a fundamental regulator of almost every process in the cell, in every tissue in the body. However, it is not certain how many of these proposed substrates are regulated by GSK3 in vivo. Clearly, the identification of the physiological functions of GSK3 will be greatly aided by the identification of its bona fide substrates, and the development of GSK3 as a therapeutic target will be highly influenced by this range of actions, hence the need to accurately establish true GSK3 substrates in cells. In this paper the evidence that proposed GSK3 substrates are likely to be physiological targets is assessed, highlighting the key cellular processes that could be modulated by GSK3 activity and inhibition.

      Related collections

      Most cited references 268

      • Record: found
      • Abstract: found
      • Article: not found

      Wnt/beta-catenin signaling: components, mechanisms, and diseases.

      Signaling by the Wnt family of secreted glycolipoproteins via the transcriptional coactivator beta-catenin controls embryonic development and adult homeostasis. Here we review recent progress in this so-called canonical Wnt signaling pathway. We discuss Wnt ligands, agonists, and antagonists, and their interactions with Wnt receptors. We also dissect critical events that regulate beta-catenin stability, from Wnt receptors to the cytoplasmic beta-catenin destruction complex, and nuclear machinery that mediates beta-catenin-dependent transcription. Finally, we highlight some key aspects of Wnt/beta-catenin signaling in human diseases including congenital malformations, cancer, and osteoporosis, and discuss potential therapeutic implications.
        Bookmark
        • Record: found
        • Abstract: found
        • Article: not found

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

        Glycogen synthase kinase-3 (GSK3) is implicated in the regulation of several physiological processes, including the control of glycogen and protein synthesis by insulin, modulation of the transcription factors AP-1 and CREB, the specification of cell fate in Drosophila and dorsoventral patterning in Xenopus embryos. GSK3 is inhibited by serine phosphorylation in response to insulin or growth factors and in vitro by either MAP kinase-activated protein (MAPKAP) kinase-1 (also known as p90rsk) or p70 ribosomal S6 kinase (p70S6k). 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.
          Bookmark
          • Record: found
          • Abstract: not found
          • Article: not found

          Alzheimer's disease: the amyloid cascade hypothesis.

            Bookmark

            Author and article information

            Affiliations
            Biomedical Research Institute, University of Dundee, Dundee DD1 9SY, UK
            Author notes

            Academic Editor: Adam Cole

            Journal
            Int J Alzheimers Dis
            IJAD
            International Journal of Alzheimer's Disease
            SAGE-Hindawi Access to Research
            2090-0252
            2011
            18 May 2011
            : 2011
            3100594
            21629754
            10.4061/2011/505607
            Copyright © 2011 Calum Sutherland.

            This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

            Categories
            Review Article

            Neurology

            Comments

            Comment on this article