Differential regulation of glycogen synthase kinase 3β by insulin and Wnt signaling
Differential regulation of glycogen synthase kinase 3β by insulin and Wnt signaling
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DOI：
10.1074/jbc.m005342200
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发表时间：
2000-10-20
影响因子：
4.8
通讯作者：
McCormick, F
中科院分区：
文献类型：
--
作者：
Ding, VW;Chen, RH;McCormick, F
糖原合成酶激酶 3 beta (GSK3 beta) 是包括胰岛素和 Wnt 信号传导在内的许多生物过程的关键组成部分。由于每个信号通路的激活都会导致 GSK3 β 活性降低，因此我们检查了它们在同一细胞类型中下游效应的特异性。胰岛素诱导糖原合酶活性增加，但对 β-连环蛋白的蛋白质水平没有影响。相反，Wnt 增加了 β-连环蛋白的胞质库，但不增加糖原合酶活性。我们发现，与胰岛素不同，GSK3β 的丝氨酸 9 残基的磷酸化状态和蛋白激酶 B 的活性均不受 Wnt 调节。尽管 GSK3 β 活性的降低是必需的，但 GSK3 β 可能不是我们检查的细胞中 Wnt 信号传导的限制成分。我们的结果表明轴蛋白-传导蛋白复合物 GSK3 β 可能专用于 Wnt 而不是胰岛素信号传导。胰岛素和 Wnt 通路通过不同的机制调节 GSK3 beta，因此导致不同的下游事件。
Glycogen synthase kinase 3 beta (GSK3 beta) is a key component in many biological processes including insulin and Wnt signaling. Since the activation of each signaling pathway results in a decrease in GSK3 beta activity, we examined the specificity of their downstream effects in the same cell type. Insulin induces an increased activity of glycogen synthase but has no influence on the protein level of beta -catenin. In contrast, Wnt increases the cytosolic pool of beta -catenin but not glycogen synthase activity. We found that, unlike insulin, neither the phosphorylation status of the serine9 residue of GSK3 beta nor the activity of protein kinase B is regulated by Wnt. Although the decrease in GSK3 beta activity is required, GSK3 beta may not be the limiting component for Wnt signaling in the cells that we examined. Our results suggest that the axin-conductin complexed GSK3 beta may be dedicated to Wnt rather than insulin signaling. Insulin and Wnt pathways regulate GSK3 beta through different mechanisms, and therefore lead to distinct downstream events.