Casein kinase I transduces Wnt signals

Abstract

The Wnt signalling cascade is essential for the development of both invertebrates and vertebrates, and is altered during tumorigenesis. Although a general framework for Wnt signalling has been elucidated, not all of the components have been identified. Here we describe a serine kinase, casein kinase I (CKI), which was isolated by expression cloning in Xenopus embryos. CKI reproduces several properties of Wnt signals, including generation of complete dorsal axes, stabilization of beta-catenin and induction of genes that are direct targets of Wnt signals. Dominant-negative forms of CKI and a pharmacological blocker of CKI inhibited Wnt signals in Xenopus. Inhibiting CKI in Caenorhabditis elegans generated worms with a mom phenotype, indicative of a loss of Wnt signals. In addition, CKI bound to and increased the phosphorylation of dishevelled, a known component of the Wnt pathway. These data indicate that CKI may be a conserved component of the Wnt pathway.

Frizzled and LRP5/6 Receptors for Wnt/ -Catenin Signaling

“…However, evidence exists that the DEP domain influences b-catenin signaling (Wong et al 2000;Simons et al 2009;Tauriello et al 2012). DVL associates with kinases such as CK11 and CK2, and becomes hyperphosphorylated upon Wnt signaling (Willert et al 1997;Peters et al 1999;Kishida et al 2001;Cong et al 2004a;Klein et al 2006). These kinases, in particular CK11, have been documented to have activating roles in Wnt/b-catenin signaling, but the role of DVL phosphorylation remains unclear.…”

-Catenin-Dependent Wnt Signaling in C. elegans: Teaching an Old Dog a New Trick

“…Genes encoding the core b-catenin destruction complex components CK1a (kin-19) (Peters et al 1999), GSK3b (gsk-3) (Schlesinger et al 1999), Axin ( pry-1 and axl-1) Korswagen et al 2002;Oosterveen et al 2007), and APC (apr-1) (Rocheleau et al 1997) are found in C. elegans. In the case of Axin and APC, the encoded proteins are fairly diverged from family members in other species, with several conserved domains absent.…”

Arabidopsis casein kinase 1-like 2 involved in abscisic acid signal transduction pathways

“…Interestingly, the CK1 family shows a strong preference both in vitro and in vivo for 'primed,' pre-phosphorylated substrates (Cheong & Virshup 2011). Considering the broad distribution of CK1 family members and their substrates, these kinases have been found to participate in many biological activities, such as Wnt signaling (Peters et al 1999;Price 2006), biological rhythm (Etchegaray et al 2009;Lee et al 2009), DNA repair (Dhillon & Hoekstra 1994), and the cell cycle (Behrend et al 2000;Petronczki et al 2006). The Arabidopsis thaliana genome was found to contain 14 casein kinase 1-like (CKL) genes, and, within the conserved kinase domains, they share 89% sequence similarity at the aa level.…”