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

ABSTRACT: 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-3? and Gsk-3?, and in general, Gsk-3 is a negative regulator of cellular signaling. Genetic deletion of both Gsk-3? and Gsk-3? in mouse embryonic stem cells (ESCs) has previously been shown to lead to the constitutive activation of the Wnt/?-catenin signaling pathway. However, in addition to Wnt signaling, all Gsk-3-regulated pathways, such as insulin signaling, are also affected simultaneously in Gsk-3?(-) (/) (-); Gsk-3?(-) (/) (-)ESCs. In an effort to better understand how specific signaling pathways contribute to the global pattern of gene expression in Gsk-3?(-) (/) (-); Gsk-3?(-) (/) (-)ESCs, we compared the gene expression profiles in Gsk-3?(-) (/) (-); Gsk-3?(-) (/) (-) ESCs to mouse ESCs in which either Wnt/?-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-3?(-) (/) (-); Gsk-3?(-) (/) (-)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.

SUBMITTER: Bartman CM 

PROVIDER: S-EPMC4131280 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature