Inhibition of GSK3beta enhances both adhesive and signalling activities of beta-catenin in mouse embryonic stem cells

Biology of the Cell
Galina S Sineva, Valery A Pospelov

Abstract

GSK3beta (glycogen synthase kinase 3beta) regulates the expression level and activity of various target proteins, including beta-catenin. beta-Catenin is a co-activator of Wnt-dependent genes as well as a partner for transmembrane cadherins to mediate cell-to-cell adhesion. In some cases, inhibition of GSK3beta activity was shown to promote self-renewal of ESCs (embryonic stem cells), but immediate effects of GSK3beta inhibitors in these cells still remain elusive. Here, we address the effects of GSK3beta inhibitors BIO (6-bromoindirubin-3'-oxime) and CHIR99021 on mESCs (mouse ESCs), focusing on modulation of beta-catenin activities. We found that, upon GSK3beta inhibition, the colonies of undifferentiated mESCs acquire a more compact morphology. This change is paralleled by two somewhat polar effects: (i) the accumulation of the beta-catenin, which is co-localized with E-cadherin at the plasma membrane, and the cytoplasmic, tyrosine unphosphorylated beta-catenin, which is able to bind the GST (glutathione transferase)-fused cytoplasmic domain of E-cadherin; and (ii) the accumulation of the tyrosine phosphorylated beta-catenin and its nuclear translocation that is accompanied by activation of the Tcf (T-cell factor)/beta-cateni...Continue Reading

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Citations

Feb 22, 2012·Stem Cells and Development·Jared M CampbellMichelle Lane
Sep 22, 2012·Stem Cells and Development·Nadejda V MezentsevaLeonard M Eisenberg
Apr 5, 2013·Journal of Tissue Engineering and Regenerative Medicine·Michael D Hoffman, Danielle S W Benoit
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Oct 27, 2020·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Vishal DeshmukhYusuf Yazici
Jan 12, 2017·Science Signaling·Iris AugustinMichael Boutros

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