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.
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.
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DOI：
10.3389/fendo.2014.00133
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发表时间：
2014
影响因子：
5.2
通讯作者：
Phiel CJ
中科院分区：
文献类型：
--
作者：
Bartman CM;Egelston J;Kattula S;Zeidner LC;D'Ippolito A;Doble BW;Phiel CJ
糖原合成酶激酶-3（Glycogen synthase kinase-3，Gsk-3）活性是众多信号转导途径的重要调节因子。Gsk-3活性是两种大量冗余蛋白Gsk-3α和Gsk-3β的总和，一般来说，Gsk-3是细胞信号传导的负调节剂。小鼠胚胎干细胞（ESC）中GSK-3α和GSK-3β的基因缺失先前已被证明导致Wnt/β-连环蛋白信号通路的组成性激活。然而，除了Wnt信号，所有Gsk-3调节的途径，如胰岛素信号，也同时在Gsk-3α−/−; Gsk-3β−/−ESCs中受到影响。为了更好地理解特定的信号通路如何影响Gsk-3α−/−; Gsk-3β−/−ESCs中基因表达的整体模式，我们将Gsk-3α−/−; Gsk-3β−/− ESCs中的基因表达谱与小鼠ESCs中的基因表达谱进行了比较，在小鼠ESCs中，Wnt/β-连环蛋白信号或磷脂酰肌醇3-激酶（PI 3 K）依赖的胰岛素信号是组成性激活的。我们的研究结果表明，Wnt信号对Gsk-3α−/−; Gsk-3β−/−ESCs中上调的基因有更大的影响，而PI 3 K依赖性胰岛素信号对相同细胞中基因的下调更负责任。这些数据显示了GSK-3活性对小鼠胚胎干细胞基因表达的重要性，这些作用是由于多种信号通路的综合作用。
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.
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影响因子：
3.7
作者：
Barrell WB;Szabo-Rogers HL;Liu KJ
通讯作者：
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影响因子：
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影响因子：
14.9
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通讯作者：
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