The casein kinase I family in Wnt signaling
The casein kinase I family in Wnt signaling
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DOI：
10.1006/dbio.2001.0308
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发表时间：
2001-07-15
影响因子：
2.7
通讯作者：
Graff, JM
中科院分区：
文献类型：
--
作者：
McKay, RM;Peters, JM;Graff, JM
经典的 Wnt 信号通路对于发育的许多方面都至关重要，Wnt 通路成分的突变具有致癌性。最近，充分性测试确定酪蛋白激酶 I epsilon (CKI epsilon) 是经典 Wnt/β-catenin 通路的阳性成分，必要性测试表明脊椎动物需要 CKIe 来转导 Wnt 信号。除了 CKI epsilon 之外，CKI 家族还包括其他几种亚型（α、β、γ 和 δ），它们在 Wnt 充分性测试中的作用尚未阐明。然而，在秀丽隐杆线虫研究中，与 CW 最相似的 CKI 同工型的功能丧失产生了 mom 表型，表明 Wnt 信号传导丧失。在本报告中，我们检查了各种 CKI 同工型激活 Wnt 信号传导的能力，发现所有野生型 CKI 同工型都具有这种功能。 Disheveled (Dsh) 是 Wnt 通路的另一个正成分，响应 Wnt 信号而被磷酸化。除 γ 外，所有 CKI 同工型都会增加体内 Dsh 的磷酸化。此外，CKI 在体外直接磷酸化 Dsh。最后，我们发现体内 Wnt 依赖性 Dsh 磷酸化需要 CKI。这些研究增进了我们对 Wnt 作用机制的理解，并表明不止一种 CKI 同工型能够在体内转导 Wnt 信号。 (C) 2001 年学术出版社。
The canonical Wnt-signaling pathway is critical for many aspects of development, and mutations in components of the Wnt pathway are carcinogenic. Recently, sufficiency tests identified casein kinase I epsilon (CKI epsilon) as a positive component of the canonical wnt/beta -catenin pathway, and necessity tests showed that CKIe is required in vertebrates to transduce Wnt signals. In addition to CKI epsilon, the CKI family includes several other isoforms (alpha, beta, gamma ,and delta) and their role in Wnt sufficiency tests had not yet been clarified. However, in Caenorhabditis elegans studies, loss-of-function of a CKI isoform most similar to cw produced the mom phenotype, indicative of loss-of-Wnt signaling. In this report, we examine the ability of the various CKI isoforms to activate Wnt signaling and find that all the wild-type CKI isoforms do so. Dishevelled (Dsh), another positive component of the Wnt pathway, becomes phosphorylated in response to Wnt signals. All the CKI isoforms, with the exception of gamma, increase the phosphorylation of Dsh in vivo. In addition, CKI directly phosphorylates Dsh in vitro. Finally, we find that CKI is required in vivo for the Wnt-dependent phosphorylation of Dsh. These studies advance our understanding of the mechanism of Wnt action and suggest that more than one CKI isoform is capable of transducing Wnt signals in vivo. (C) 2001 Academic Press.