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J Biol Chem. 2014 Sep 19;289(38):26344-56. doi: 10.1074/jbc.M114.562165. Epub 2014 Aug 6.

Casein kinase 1 α phosphorylates the Wnt regulator Jade-1 and modulates its activity.

Author information

1
From the Department II of Internal Medicine and Center for Molecular Medicine Cologne.
2
From the Department II of Internal Medicine and Center for Molecular Medicine Cologne, Cologne Excellence Cluster on Cellular Stress Responses in Aging-associated Diseases (CECAD), and.
3
the Renal Division, Department of Medicine, University of Freiburg Medical Center, 79106 Freiburg, Germany, and.
4
Cologne Excellence Cluster on Cellular Stress Responses in Aging-associated Diseases (CECAD), and.
5
the Renal Division, Department of Medicine, University of Freiburg Medical Center, 79106 Freiburg, Germany, and the Center for Biological Signaling Studies (BIOSS), Albert Ludwigs University, 79108 Freiburg, Germany.
6
From the Department II of Internal Medicine and Center for Molecular Medicine Cologne, Cologne Excellence Cluster on Cellular Stress Responses in Aging-associated Diseases (CECAD), and Systems Biology of Ageing Cologne, University of Cologne, 50931 Cologne, Germany.
7
From the Department II of Internal Medicine and Center for Molecular Medicine Cologne, Cologne Excellence Cluster on Cellular Stress Responses in Aging-associated Diseases (CECAD), and Systems Biology of Ageing Cologne, University of Cologne, 50931 Cologne, Germany, bernhard.schermer@uk-koeln.de.

Abstract

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.

KEYWORDS:

Casein Kinase 1 α; Centrosome; Cilia; NPHP4; Phosphorylation; Wnt Signaling; β-catenin (B-catenin)

PMID:
25100726
PMCID:
PMC4176241
DOI:
10.1074/jbc.M114.562165
[Indexed for MEDLINE]
Free PMC Article

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