Unwinding the Wnt action of casein kinase 1  

作　　者：Daniel GR Yim David M Virshup 

机构地区：[1]Program in Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School Singapore, Singapore [2]Graduate School for IntegrativeSciences and Engineering, National UniversiO,of Singapore, Singapore

出　　处：《Cell Research》2013年第6期737-738,共2页细胞研究（英文版）

摘　　要：The casein kinase 1 （CK1） family, a major intracellular serine/threo nine kinase, is implicated in multiple pathways; however, understanding its regulation has proven challenging. A recent study published in Science identifying allosteric activation of CK1 by the DEADbox RNA helicase DDX3 expands our understanding of the control of this abundant kinase family. The human CK1 protein kinase family is encoded by six genes （ct, T1, 72, 73, 6, and e） and regulates diverse biochemical processes including hedge hog signaling, circadian rhythms and the p53 tumor suppression [reviewed in 1]. In the Wnt/βcatenin pathway, all CK1 family members are involved, each with a distinct role. To carry out their functions, CK1 family members achieve specificity by several mechanisms, but how their kinase activity is regulated has been less clear. Here, we discuss the findings of the Niehrs lab [2] in the context of what is known about CK1 control in the Wnt pathway. CK17 proteins are membrane bound due to Cterminal Spalmitoylation and phosphorylate the Wnt coreceptor LRP5/6 in the presence of Wnts and Disheveled to activate the pathway [3, 4]. One mechanism of activation may be via ＇priming＇ by upstream phosphoryla tion ofLRP5/6, a common characteristic ofCK1 substrate recognition [5]. CK18 and CK1 e bind to and phosphorylate Di sheveled, an activity regulated by Wnt signaling and protein phosphatases [6, 7]. CK1 ~ interacts with and phosphory lates APC, Axin and Ser45 of βcatenin in an apparently unregulated reaction. The CKlctcatalyzed phosphorylationprimes flcatenin for further phosphory lation by GSK3 and subsequent degra dation. How does CK1 accomplish so many different jobs in the Wnt pathway and how is it controlled？ A key mechanism for regulation is CK 1 s＇ differential interaction with scaf folds and membranes. CK16 and CKle bind to substrates including Disheveled, Period and NFAT 1; CK 1 ct interacts with Axin, and CK17 localizes to membranes where it phosphorylates LRP6. These interactions take place

关 键 词：Wnt信号通路 酪蛋白激酶 磷酸化位点 蛋白激酶活性 Wnt信号传导 监管机制 家庭成员 蛋白磷酸酶 

分 类 号：Q2[生物学—细胞生物学] Q26