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Casein kinase 1 α phosphorylates the Wnt regulator Jade-1 and modulates its activity.
Borgal L
,
Rinschen MM
,
Dafinger C
,
Hoff S
,
Reinert MJ
,
Lamkemeyer T
,
Lienkamp SS
,
Benzing T
,
Schermer B
.
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Tight regulation of Wnt/β-catenin signaling is critical for vertebrate development and tissue maintenance, and deregulation can lead to a host of disease phenotypes, including developmental disorders and cancer. Proteins associated with primary cilia and centrosomes have been demonstrated to negatively regulate canonical Wnt signaling in interphase cells. The plant homeodomain zinc finger protein Jade-1 can act as an E3 ubiquitin ligase-targeting β-catenin for proteasomal degradation and concentrates at the centrosome and ciliary basal body in addition to the nucleus in interphase cells. We demonstrate that the destruction complex component casein kinase 1α (CK1α) phosphorylates Jade-1 at a conserved SLS motif and reduces the ability of Jade-1 to inhibit β-catenin signaling. Consistently, Jade-1 lacking the SLS motif is more effective than wild-type Jade-1 in reducing β-catenin-induced secondary axis formation in Xenopus laevis embryos in vivo. Interestingly, CK1α also phosphorylates β-catenin and the destruction complex component adenomatous polyposis coli at a similar SLS motif to the effect that β-catenin is targeted for degradation. The opposing effect of Jade-1 phosphorylation by CK1α suggests a novel example of the dual functions of CK1α activity to either oppose or promote canonical Wnt signaling in a context-dependent manner.
Anastas,
WNT signalling pathways as therapeutic targets in cancer.
2013, Pubmed
Anastas,
WNT signalling pathways as therapeutic targets in cancer.
2013,
Pubmed
Baron,
WNT signaling in bone homeostasis and disease: from human mutations to treatments.
2013,
Pubmed
Benzing,
Nephrocystin interacts with Pyk2, p130(Cas), and tensin and triggers phosphorylation of Pyk2.
2001,
Pubmed
Borgal,
The ciliary protein nephrocystin-4 translocates the canonical Wnt regulator Jade-1 to the nucleus to negatively regulate β-catenin signaling.
2012,
Pubmed
Brockman,
Cell cycle-dependent localization of casein kinase I to mitotic spindles.
1992,
Pubmed
Chen,
Regulation of p53-MDMX interaction by casein kinase 1 alpha.
2005,
Pubmed
Chilov,
Phosphorylated β-catenin localizes to centrosomes of neuronal progenitors and is required for cell polarity and neurogenesis in developing midbrain.
2011,
Pubmed
Chitalia,
Jade-1 inhibits Wnt signalling by ubiquitylating beta-catenin and mediates Wnt pathway inhibition by pVHL.
2008,
Pubmed
,
Xenbase
Choo,
Detection of protein ubiquitination.
2009,
Pubmed
Clevers,
Wnt/beta-catenin signaling in development and disease.
2006,
Pubmed
Clevers,
Wnt/β-catenin signaling and disease.
2012,
Pubmed
Corbit,
Kif3a constrains beta-catenin-dependent Wnt signalling through dual ciliary and non-ciliary mechanisms.
2008,
Pubmed
Cox,
MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification.
2008,
Pubmed
Cox,
Accurate proteome-wide label-free quantification by delayed normalization and maximal peptide ratio extraction, termed MaxLFQ.
2014,
Pubmed
Dale,
Kinase cogs go forward and reverse in the Wnt signaling machine.
2006,
Pubmed
Del Valle-Pérez,
Coordinated action of CK1 isoforms in canonical Wnt signaling.
2011,
Pubmed
Delous,
Nephrocystin-1 and nephrocystin-4 are required for epithelial morphogenesis and associate with PALS1/PATJ and Par6.
2009,
Pubmed
Ferrarese,
Chemical dissection of the APC Repeat 3 multistep phosphorylation by the concerted action of protein kinases CK1 and GSK3.
2007,
Pubmed
Flotow,
Phosphate groups as substrate determinants for casein kinase I action.
1990,
Pubmed
Flozak,
Beta-catenin/T-cell factor signaling is activated during lung injury and promotes the survival and migration of alveolar epithelial cells.
2010,
Pubmed
Fumoto,
Axin localizes to the centrosome and is involved in microtubule nucleation.
2009,
Pubmed
Gerdes,
Disruption of the basal body compromises proteasomal function and perturbs intracellular Wnt response.
2007,
Pubmed
Goentoro,
Evidence that fold-change, and not absolute level, of beta-catenin dictates Wnt signaling.
2009,
Pubmed
,
Xenbase
González-Sancho,
The Wnt antagonist DICKKOPF-1 gene is a downstream target of beta-catenin/TCF and is downregulated in human colon cancer.
2005,
Pubmed
Greer,
Casein kinase 1 delta functions at the centrosome to mediate Wnt-3a-dependent neurite outgrowth.
2011,
Pubmed
Ha,
Mechanism of phosphorylation-dependent binding of APC to beta-catenin and its role in beta-catenin degradation.
2004,
Pubmed
Habbig,
NPHP4, a cilia-associated protein, negatively regulates the Hippo pathway.
2011,
Pubmed
Hikasa,
Wnt signaling in vertebrate axis specification.
2013,
Pubmed
,
Xenbase
Hoff,
ANKS6 is a central component of a nephronophthisis module linking NEK8 to INVS and NPHP3.
2013,
Pubmed
,
Xenbase
Hoffert,
An automated platform for analysis of phosphoproteomic datasets: application to kidney collecting duct phosphoproteins.
2007,
Pubmed
Inestrosa,
Emerging roles of Wnts in the adult nervous system.
2010,
Pubmed
Ishibe,
Epithelial-mesenchymal-epithelial cycling in kidney repair.
2008,
Pubmed
Jho,
Wnt/beta-catenin/Tcf signaling induces the transcription of Axin2, a negative regulator of the signaling pathway.
2002,
Pubmed
Kawakami,
Wnt signalling in kidney diseases: dual roles in renal injury and repair.
2013,
Pubmed
Koch,
The Wnt antagonist Dkk1 regulates intestinal epithelial homeostasis and wound repair.
2011,
Pubmed
Kühl,
On the role of Wnt/β-catenin signaling in stem cells.
2013,
Pubmed
Lancaster,
Subcellular spatial regulation of canonical Wnt signalling at the primary cilium.
2011,
Pubmed
Li,
Wnt signaling through inhibition of β-catenin degradation in an intact Axin1 complex.
2012,
Pubmed
Liu,
Mammalian casein kinase 1alpha and its leishmanial ortholog regulate stability of IFNAR1 and type I interferon signaling.
2009,
Pubmed
Logan,
The Wnt signaling pathway in development and disease.
2004,
Pubmed
Lustig,
Negative feedback loop of Wnt signaling through upregulation of conductin/axin2 in colorectal and liver tumors.
2002,
Pubmed
Marin,
A noncanonical sequence phosphorylated by casein kinase 1 in beta-catenin may play a role in casein kinase 1 targeting of important signaling proteins.
2003,
Pubmed
Marin,
Phosphorylation of synthetic fragments of inhibitor-2 of protein phosphatase-1 by casein kinase-1 and -2. Evidence that phosphorylated residues are not strictly required for efficient targeting by casein kinase-1.
1994,
Pubmed
Meggio,
A synthetic beta-casein phosphopeptide and analogues as model substrates for casein kinase-1, a ubiquitous, phosphate directed protein kinase.
1991,
Pubmed
Mollet,
Characterization of the nephrocystin/nephrocystin-4 complex and subcellular localization of nephrocystin-4 to primary cilia and centrosomes.
2005,
Pubmed
Nagaraj,
Feasibility of large-scale phosphoproteomics with higher energy collisional dissociation fragmentation.
2010,
Pubmed
Nejak-Bowen,
Beta-catenin signaling, liver regeneration and hepatocellular cancer: sorting the good from the bad.
2011,
Pubmed
Niida,
DKK1, a negative regulator of Wnt signaling, is a target of the beta-catenin/TCF pathway.
2004,
Pubmed
Osakada,
Wnt signaling promotes regeneration in the retina of adult mammals.
2007,
Pubmed
Perez-Moreno,
Catenins: keeping cells from getting their signals crossed.
2006,
Pubmed
Peters,
Casein kinase I transduces Wnt signals.
1999,
Pubmed
,
Xenbase
Pulgar,
Optimal sequences for non-phosphate-directed phosphorylation by protein kinase CK1 (casein kinase-1)--a re-evaluation.
1999,
Pubmed
,
Xenbase
Rena,
D4476, a cell-permeant inhibitor of CK1, suppresses the site-specific phosphorylation and nuclear exclusion of FOXO1a.
2004,
Pubmed
Reya,
Wnt signalling in stem cells and cancer.
2005,
Pubmed
Rinschen,
Quantitative phosphoproteomic analysis reveals vasopressin V2-receptor-dependent signaling pathways in renal collecting duct cells.
2010,
Pubmed
Rinschen,
Phosphoproteomic analysis reveals regulatory mechanisms at the kidney filtration barrier.
2014,
Pubmed
Schermer,
Phosphorylation by casein kinase 2 induces PACS-1 binding of nephrocystin and targeting to cilia.
2005,
Pubmed
Silkstone,
Beta-catenin in the race to fracture repair: in it to Wnt.
2008,
Pubmed
Thakur,
Pharmacological modulation of beta-catenin and its applications in cancer therapy.
2013,
Pubmed
Wang,
Automated quantification tool for high-throughput proteomics using stable isotope labeling and LC-MSn.
2006,
Pubmed
Yamamoto,
Heparan sulfate on intestinal epithelial cells plays a critical role in intestinal crypt homeostasis via Wnt/β-catenin signaling.
2013,
Pubmed
Zeng,
A dual-kinase mechanism for Wnt co-receptor phosphorylation and activation.
2005,
Pubmed
,
Xenbase
