Gene Expression Profiling in Mouse Embryonic Stem Cells Reveals Glycogen Synthase Kinase-3-Dependent Targets of Phosphatidylinositol 3-Kinase and Wnt/β-Catenin Signaling Pathways

Glycogen synthase kinase-3 (Gsk-3) activity is an important regulator of numerous signal transduction pathways. Gsk-3 activity is the sum of two largely redundant proteins, Gsk-3α and Gsk-3β, and in general, Gsk-3 is a negative regulator of cellular signaling. Genetic deletion of both Gsk-3α and Gsk...

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Published in:Frontiers in endocrinology (Lausanne) 2014-01, Vol.5, p.133-133
Main Authors: Bartman, Colleen M, Egelston, Jennifer, Kattula, Sravya, Zeidner, Leigh C, D'Ippolito, Anthony, Doble, Bradley W, Phiel, Christopher J
Format: Article
Language:English
Subjects:
Embryonic Stem Cells
Endocrinology
Gene Expression
Microarray
Phosphatidylinositol 3-Kinase
Signal Transduction
Wnt
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Summary:Glycogen synthase kinase-3 (Gsk-3) activity is an important regulator of numerous signal transduction pathways. Gsk-3 activity is the sum of two largely redundant proteins, Gsk-3α and Gsk-3β, and in general, Gsk-3 is a negative regulator of cellular signaling. Genetic deletion of both Gsk-3α and Gsk-3β in mouse embryonic stem cells (ESCs) has previously been shown to lead to the constitutive activation of the Wnt/β-catenin signaling pathway. However, in addition to Wnt signaling, all Gsk-3-regulated pathways, such as insulin signaling, are also affected simultaneously in Gsk-3α(-) (/) (-); Gsk-3β(-) (/) (-)ESCs. In an effort to better understand how specific signaling pathways contribute to the global pattern of gene expression in Gsk-3α(-) (/) (-); Gsk-3β(-) (/) (-)ESCs, we compared the gene expression profiles in Gsk-3α(-) (/) (-); Gsk-3β(-) (/) (-) ESCs to mouse ESCs in which either Wnt/β-catenin signaling or phosphatidylinositol 3-kinase (PI3K)-dependent insulin signaling are constitutively active. Our results show that Wnt signaling has a greater effect on up-regulated genes in the Gsk-3α(-) (/) (-); Gsk-3β(-) (/) (-)ESCs, whereas PI3K-dependent insulin signaling is more responsible for the down-regulation of genes in the same cells. These data show the importance of Gsk-3 activity on gene expression in mouse ESCs, and that these effects are due to the combined effects of multiple signaling pathways.
ISSN:1664-2392
1664-2392
DOI:10.3389/fendo.2014.00133