Coordinated Action of CK1 Isoforms in Canonical Wnt Signaling
- 1 July 2011
- journal article
- Published by Taylor & Francis Ltd in Molecular and Cellular Biology
- Vol. 31 (14), 2877-2888
- https://doi.org/10.1128/mcb.01466-10
Abstract
Activation of the Wnt pathway promotes the progressive phosphorylation of coreceptor LRP5/6 (low-density lipoprotein receptor-related proteins 5 and 6), creating a phosphorylated motif that inhibits glycogen synthase kinase 3β (GSK-3β), which in turn stabilizes β-catenin, increasing the transcription of β-catenin target genes. Casein kinase 1 (CK1) kinase family members play a complex role in this pathway, either as inhibitors or as activators. In this report, we have dissected the roles of CK1 isoforms in the early steps of Wnt signaling. CK1ε is constitutively bound to LRP5/6 through its interaction with p120-catenin and E-cadherin or N-cadherin and is activated upon Wnt3a stimulation. CK1α also associates with the LRP5/6/p120-catenin complex but, differently from CK1ε, only after Wnt3a addition. Binding of CK1α is dependent on CK1ε and occurs in a complex with axin. The two protein kinases function sequentially: whereas CK1ε is required for early responses to Wnt3a stimulation, such as recruitment of Dishevelled 2 (Dvl-2), CK1α participates in the release of p120-catenin from the complex, which activates p120-catenin for further actions on this pathway. Another CK1, CK1γ, acts at an intermediate level, since it is not necessary for Dvl-2 recruitment but for LRP5/6 phosphorylation at Thr1479 and axin binding. Therefore, our results indicate that CK1 isoforms work coordinately to promote the full response to Wnt stimulus.Keywords
This publication has 27 references indexed in Scilit:
- Wnt Signaling Requires Sequestration of Glycogen Synthase Kinase 3 inside Multivesicular EndosomesCell, 2010
- Regulation of Lrp6 phosphorylationCellular and Molecular Life Sciences, 2010
- Dab2 stabilizes Axin and attenuates Wnt/β-catenin signaling by preventing protein phosphatase 1 (PP1)–Axin interactionsOncogene, 2009
- Wnt/β-Catenin Signaling: Components, Mechanisms, and DiseasesDevelopmental Cell, 2009
- N-Cadherin Interacts with Axin and LRP5 To Negatively Regulate Wnt/β-Catenin Signaling, Osteoblast Function, and Bone FormationMolecular and Cellular Biology, 2009
- Gamma-Secretase-Dependent and -Independent Effects of Presenilin1 on β-Catenin·Tcf-4 Transcriptional ActivityPLOS ONE, 2008
- Direct Inhibition of GSK3β by the Phosphorylated Cytoplasmic Domain of LRP6 in Wnt/β-Catenin SignalingPLOS ONE, 2008
- Wnt Induces LRP6 Signalosomes and Promotes Dishevelled-Dependent LRP6 PhosphorylationScience, 2007
- Specific Phosphorylation of p120-Catenin Regulatory Domain Differently Modulates Its Binding to RhoAMolecular and Cellular Biology, 2007
- The Roles of APC and Axin Derived from Experimental and Theoretical Analysis of the Wnt PathwayPLoS Biology, 2003