Coordinated Action of CK1 Isoforms in Canonical Wnt Signaling

Valle-Pérez, Beatriz Del; Arqués, Oriol; Vinyoles, Meritxell; Herreros, Antonio Garcı́a de; Duñach, Mireia

doi:10.1128/mcb.01466-10

Cited by 71 publications

(72 citation statements)

References 28 publications

(33 reference statements)

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“…In fact, early observations that overexpression of CK1 isoforms in Xenopus embryos caused axis duplication suggested a positive role for CK1 in Wnt signalling 47. However, it has since become evident that CK1 isoforms play both negative and positive roles in the Wnt/β‐catenin signalling 29, and their activities may be regulated in a coordinated fashion 48. The precise mechanisms by which CK1 isoforms are regulated to allow them to execute these opposing outcomes in Wnt/β‐catenin signalling remain elusive.…”

Section: Discussionmentioning

confidence: 99%

PAWS 1 controls Wnt signalling through association with casein kinase 1α

Bozatzi

Dingwell

et al. 2018

EMBO Reports

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The BMP and Wnt signalling pathways determine axis specification during embryonic development. Our previous work has shown that PAWS1 (also known as FAM83G) interacts with SMAD1 and modulates BMP signalling. Here, surprisingly, we show that overexpression of PAWS1 in Xenopus embryos activates Wnt signalling and causes complete axis duplication. Consistent with these observations in Xenopus, Wnt signalling is diminished in U2OS osteosarcoma cells lacking PAWS1, while BMP signalling is unaffected. We show that PAWS1 interacts and co‐localises with the α isoform of casein kinase 1 (CK1), and that PAWS1 mutations incapable of binding CK1 fail both to activate Wnt signalling and to elicit axis duplication in Xenopus embryos.

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Section: Discussionmentioning

confidence: 99%

PAWS 1 controls Wnt signalling through association with casein kinase 1α

Bozatzi

Dingwell

et al. 2018

EMBO Reports

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“…Indeed, the transmembrane protein TMEM198 enhances LRP6 signaling and phosphorylation by CK1 through its binding to CK1a, 1, and g . Efforts have been taken to distinguish roles of different CK1s in multiple steps in Wnt signaling (Del Valle-Perez et al 2011), but the available evidence suggests overlapping functions of CK1s in LRP6 phosphorylation.…”

Section: Lrp6 Phosphorylation: Kinases and Regulationmentioning

confidence: 99%

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

MacDonald

2012

Cold Spring Harbor Perspectives in Biology

495

411

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Frizzled and LRP5/6 are Wnt receptors that upon activation lead to stabilization of cytoplasmic b-catenin. In this study, we review the current knowledge of these two families of receptors, including their structures and interactions with Wnt proteins, and signaling mechanisms from receptor activation to the engagement of intracellular partners Dishevelled and Axin, and finally to the inhibition of b-catenin phosphorylation and ensuing b-catenin stabilization.T he Wnt/b-catenin pathway, or canonical Wnt pathway as it is often referred to, is an ancient and conserved signaling cascade involving b-catenin acting as a transcriptional coactivator (Logan and Nusse 2004). The pathway is best understood when considered in a two-state model of OFF (without Wnt) and ON (with Wnt). In the OFF state, cytoplasmic b-catenin is constitutively targeted for degradation by two multidomain scaffolding proteins, Axin and Adenomatous polyposis coli (APC), which facilitate the amino-terminal phosphorylation of b-catenin via the kinases GSK3 and CKIa. Phosphorylated b-catenin is recognized by the E3 ubiquitin ligase b-Trcp and is thus ubiquitinated and degraded by the proteasome, thereby maintaining low levels of free b-catenin in the cytoplasm and nucleus (MacDonald et al. 2009). In the ON state, a Wnt ligand binds to the seven-pass transmembrane receptor Frizzled (FZD) and the single-pass low-density lipoprotein receptor-related protein 5 or 6 (LRP5/6) ). The Wnt-FZD -LRP5/6 trimeric complex recruits Dishevelled (DVL) and Axin through the intracellular domains of FZD and LRP5/6, resulting in inhibition of b-catenin phosphorylation and thus ensuing b-catenin stabilization. The rise of cytoplasmic and nuclear levels of b-catenin levels promotes b-catenin partnering with the TCF/ LEF transcription factors for activation of Wntresponsive gene expression.Wnt/b-catenin signaling controls cell proliferation and differentiation and is a key regulatory mechanism for stem cells. As such, mutations in the Wnt pathway cause many diseases including cancer (Clevers 2006). All of the above "core" Wnt/b-catenin signaling components are present in vertebrates and the well-studied fruit fly Drosophila and are also encoded in sequenced genomes of radial symmetric Cnidarians Hydra magnipapillata and Nematostella vectensis (Guder et al. 2006) and of the primitive metazoan sponge Amphimedon queenslandica

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“…Together with Axin, two kinases -GSK3 and the primer kinases CK1( , , ) -are juxtaposed with LRP5/6 [230]. CK1-mediated phosphorylation acts as primer, which triggers GSK3-mediated phosphorylation.…”

Section: The Wnt Receptor Complexmentioning

confidence: 99%

“…One model suggested that phosphorylation of Dishevelled-2 by CK1 increases its affinity to Frizzled receptors [219,233]. CK1 was also shown to be required for Dvl-2 phosphorylation and its binding to LRP5/6 [230]. In turn, CK1 was shown to be directly activated by Wnt signaling through C-terminal dephosphorylation [234].…”

Section: The Wnt Receptor Complexmentioning

confidence: 99%

“…Ncadherin [304] and E-cadherin [305] were shown to be able to directly associate with Lrp5/6. Binding of Wnt morphogens to the Frizzled-LRP5/6 induces a CK1 -dependent phosphorylation of both LRP5/6 and E-cadherin [306] inducing a dissociation of LRP5/6 from E-cadherin [230]. Furthermore, Wnt binding to Frizzled-LRP5/6 induces the phosphorylation of CK1 dependent phosphorylation of p120 (at Ser268 and Ser269) leading to the dissociation of p120 from the E-cadherin complex [230].…”

Section: Connections Between the Wnt-frizzled-lrp5/6 Signalosome Andmentioning

confidence: 99%

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Wnt/beta-Catenin Signaling and Small Molecule Inhibitors

Voronkov¹,

Krauß²

2012

CPD

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Wnt/ -catenin signaling is a branch of a functional network that dates back to the first metazoans and it is involved in a broad range of biological systems including stem cells, embryonic development and adult organs. Deregulation of components involved in Wnt/ -catenin signaling has been implicated in a wide spectrum of diseases including a number of cancers and degenerative diseases. The key mediator of Wnt signaling, -catenin, serves several cellular functions. It functions in a dynamic mode at multiple cellular locations, including the plasma membrane, where -catenin contributes to the stabilization of intercellular adhesive complexes, the cytoplasm where -catenin levels are regulated and the nucleus where -catenin is involved in transcriptional regulation and chromatin interactions. Central effectors of -catenin levels are a family of cysteine-rich secreted glycoproteins, known as Wnt morphogens. Through the LRP5/6-Frizzled receptor complex, Wnts regulate the location and activity of the destruction complex and consequently intracellularcatenin levels. However, -catenin levels and their effects on transcriptional programs are also influenced by multiple other factors including hypoxia, inflammation, hepatocyte growth factor-mediated signaling, and the cell adhesion molecule E-cadherin. The broad implications of Wnt/ -catenin signaling in development, in the adult body and in disease render the pathway a prime target for pharmacological research and development. The intricate regulation of -catenin at its various locations provides alternative points for therapeutic interventions.

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Coordinated Action of CK1 Isoforms in Canonical Wnt Signaling

Cited by 71 publications

References 28 publications

PAWS 1 controls Wnt signalling through association with casein kinase 1α

PAWS 1 controls Wnt signalling through association with casein kinase 1α

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

Wnt/beta-Catenin Signaling and Small Molecule Inhibitors

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