Wnt-11 signaling leads to down-regulation of the Wnt/β-catenin, JNK/AP-1 and NF-κB pathways and promotes viability in the CHO-K1 cells
Wnt-11 signaling leads to down-regulation of the Wnt/β-catenin, JNK/AP-1 and NF-κB pathways and promotes viability in the CHO-K1 cells
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DOI：
10.1016/j.yexcr.2008.04.010
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发表时间：
2008-08-01
影响因子：
3.7
通讯作者：
Vainio, Seppo
中科院分区：
文献类型：
--
作者：
Railo, Antti;Nagy, Irina I.;Vainio, Seppo
糖蛋白生长因子Wnt家族控制着许多核心细胞过程，如增殖、分化和衰老。到目前为止，所有已分析的Wnt蛋白要么激活要么抑制调节靶基因转录的经典β -连环蛋白信号通路。此外，其中一些蛋白激活非经典信号通路，涉及JNK、异源三聚体G蛋白、蛋白激酶C和钙调蛋白依赖性蛋白激酶II等成分，尽管精确的信号传导机制才刚刚开始被揭示。我们在此证明，Wnt - 11信号不仅足以抑制经典的β -连环蛋白介导的Wnt信号，还能抑制中国仓鼠卵巢（CHO）细胞中的JNK/AP - 1和NF - κB信号，因此在该系统中作为一种非经典的Wnt配体。JNK/AP - 1通路的抑制部分由丝裂原活化蛋白激酶激酶MKK4和Akt介导。此外，蛋白激酶C参与Wnt - 11对JNK/AP - 1的调节，但不参与对NF - κB通路的调节。与Akt、JNK和NF - κB在细胞存活和应激反应中的核心作用一致，Wnt - 11信号促进细胞活力。因此，Wnt - 11参与关键信号通路的协调。（c）2008爱思唯尔公司。保留所有权利。
The Wnt family of glycoprotein growth factors controls a number of central cellular processes such as proliferation, differentiation and ageing. All the Wnt proteins analyzed so far either activate or inhibit the canonical beta-catenin signaling pathway that regulates transcription of the target genes. In addition, some of them activate noncanonical signaling pathways that involve components such as the JNK, heterotrimeric G proteins, protein kinase C, and calmodulin-dependent protein kinase II, although the precise signaling mechanisms are only just beginning to be revealed. We demonstrate here that Wnt-11 signaling is sufficient to inhibit not only the canonical beta-catenin mediated Wnt signaling but also JNK/AP-1 and NF-kappa B signaling in the CHO cells, thus serving as a noncanonical Wnt ligand in this system. Inhibition of the JNK/AP-1 pathway is mediated in part by the MAPK kinase MKK4 and Akt. Moreover, protein kinase C is involved in the regulation of JNK/AP-1 by Wnt-11, but not of the NF-kappa B pathway. Consistent with the central role of Akt, JNK and NF-kappa B in cell survival and stress responses, Wnt-11 signaling promotes cell viability. Hence Wnt-11 is involved in coordination of key signaling pathways. (c) 2008 Elsevier Inc. All rights reserved.