Wnt controls the transcriptional activity of Kaiso through CK1ε-dependent phosphorylation of p120-catenin

Valle-Pérez, Beatriz Del; Casagolda, David; Lugilde, Ero; Valls, Gabriela; Codina, Montserrat; Dave, Natàlia; Herreros, Antonio Garcı́a de; Duñach, Mireia

doi:10.1242/jcs.082693

Cited by 49 publications

(62 citation statements)

References 33 publications

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“…3G, Wnt3a enhances p120-catenin interaction with Rac1 and Vav2 in SW-480 cells. This increase was accompanied by p120-catenin phosphorylation by CK1a, determined analyzing Ser268 modification (Del Valle-Pérez et al, 2011a;Del Valle-Pérez et al, 2011b). Conversely, tyrosine phosphorylation on p120-catenin was decreased by Wnt3a (Fig.…”

Section: Vav2 Interacts With P120-catenin and Is Required For Rac1 Acmentioning

confidence: 86%

“…Through its interaction with E-cadherin (or N-cadherin in mesenchymal cells), p120-catenin associates with the LRP5/6 coreceptor and enables the binding to this complex of CK1e, a protein kinase constitutively associated with p120-catenin. This catenin is required for CK1e activation and for the initial responses to Wnt3a, such as Dvl2 or LRP5/6 phosphorylation (Casagolda et al, 2010;Del Valle-Pérez et al, 2011a;Del Valle-Pérez et al, 2011b). A current model depicting our vision of this process is presented in Fig.…”

Section: Discussionmentioning

confidence: 99%

“…P values were determined using ANOVA. inhibition caused by Kaiso on the expression of several target genes (Del Valle-Pérez et al, 2011b;Kelly et al, 2004;Kim et al, 2004;Park et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

“…This E-cadherin-unbound p120-catenin plays additional roles in Wnt signaling because it interacts with Kaiso, preventing the inhibition by this factor of b-catenin/Tcf-4 complex (Del VallePérez et al, 2011b). In this article, we show that p120-catenin, when released from E-cadherin, exerts an additional action in the We have analyzed Rac1 stimulation by Wnt3a using two cellular systems: HEK-293 fibroblasts, widely used to study this signaling pathway, and SW-480 colon cells that, although mutant in APC and therefore deficient in b-catenin degradation, are totally competent for other signals triggered by this stimulus (Casagolda et al, 2010;Del Valle-Pérez et al, 2011a;Del Valle-Pérez et al, 2011b). Upon Wnt3a addition, Rac1 became stimulated in both cell lines (Fig.…”

Section: Introductionmentioning

confidence: 99%

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Rac1 activation upon Wnt stimulation requires Rac1 and Vav2 binding to p120-catenin

Valls

Codina

Miller

et al. 2012

Journal of Cell Science

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There was an error published in J. Cell Sci. 125, 5288-5301.In Fig. 2B, panels labelled as the actin input and p120-catenin IP:p120-catenin panels were inadvertently assembled to show the same blots. Concerns were also raised about possible duplications and/or splices in Figs 4A, 4E, 5D, 6A and 6C. The authors were unable to obtain the original data in order to address these concerns and therefore repeated the experiments. The new data are shown in the figures below and have been verified by the corresponding author's institute as supporting the original conclusions of the study. There are no changes to the figure legends, which are accurate.The authors acknowledge the increased contribution of Beatriz Del Valle-Pérez in repeating the experiments and apologise to the readers for any confusion that these errors might have caused. Fig. 2. Wnt-induced Rac1 activation is dependent on Vav2 interaction with p120-catenin. Vav2 (A) and p120-catenin (B) were immunoprecipitated from 500 µg SW-480 whole-cell extracts treated with control or Wnt3a-conditioned medium for the times indicated. Protein complexes were analyzed by western blot (WB) with anti-p120-catenin, anti-Vav2, anti-E-cadherin and anti-Rac1. 10 µg of SW-480 whole-cell extracts were included as internal reference (input). The graphs on the right are autoradiograms from four different experiments that were quantified and the mean ± s.d. obtained after 2 hours of incubation with Wnt3a medium. Each value is presented relative to that obtained in cells treated with control medium and normalized with respect to the amount of immunoprecipitated Vav2 or p120-catenin. (C) SW-480 cells stably expressing scrambled or shRNA specific for Vav2 were treated with control or Wnt3a-conditioned medium for 2 hours. GST-PAK pull-down assays were performed and active Rac1 was determined by WB. Autoradiograms from five different experiments performed in triplicate were quantified and the mean ± s.d. was obtained for each condition. Each value is presented relative to that obtained in nondepleted cells treated with control medium. (D) Cytosolic and nuclear lysates were obtained from control and Vav2-depleted SW-480 cells treated with control or Wnt3a-conditioned medium for 15 hours. β-catenin distribution between the two cell compartments was analyzed by WB. 2120© 2016. Published by The Company of Biologists Ltd | Journal of Cell Science (2016Science ( ) 129, 2120Science ( -2123Science ( doi:10.1242 Journal of Cell Science 480 (E,F) cells overexpressing either GFP-p120-catenin wt isoform 1, GFP-p120-catenin point mutants Y112E or Y217E or the empty vector phrGFP, treated when indicated with Wnt3a-conditioned medium for 15 hours. The nuclear fraction was separated from the cytosolic and membrane-associated fraction as detailed in Materials and Methods. β-catenin levels in each cellular fraction were analyzed by WB. Lamin-β1 was used as a nuclear marker and pyruvate kinase as a marker for the cytosolic-plus-membrane fraction. In the right panel of C, p120-catenin wt, Y112E and Y217E...

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Section: Vav2 Interacts With P120-catenin and Is Required For Rac1 Acmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Rac1 activation upon Wnt stimulation requires Rac1 and Vav2 binding to p120-catenin

Valls

Codina

Miller

et al. 2012

Journal of Cell Science

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“…A potential intersection of Kaiso with Wnt signalling pathways may occur in cancer, where over-expression of Kaiso could attenuate constitutive Wnt signalling, while at the same time promoting cancer progression through silencing of de novo methylated tumour suppressor genes (Lopes et al, 2008). Recently published work shows that disruption of the Tcf4:Kaiso interaction in human colon cancer cell lines releases Tcf4, enabling its mutual association with -catenin and the formation of a transcriptional complex (Del Valle-Perez et al, 2011). This also permits Kaiso binding to the methylated CDKN2A promoter in cells, leading to its decreased expression.…”

Section: Frog -Xenopus Tropicalis / Xenopus Laevismentioning

confidence: 99%

DNA Methylation in Mammalian and Non-Mammalian Organisms

Moffat¹,

Reddington²,

Pennings³

et al. 2012

DNA Methylation - From Genomics to Technology

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Kaiso phosphorylation at threonine 606 leads to its accumulation in the cytoplasm, reducing its transcriptional repression of the tumour suppressor CDH1

et al. 2022

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It is well known that the Kaiso protein (encoded by the ZBTB33 gene) is a transcription factor, and Kaiso–P120ctn [P120 catenin (CTNND1)] interaction increases the translocation of Kaiso from the nucleus into the cytoplasm. However, the regulatory mechanisms of Kaiso compartmentalisation are far from clear. Here, we reported that RAC‐alpha serine/threonine‐protein kinase (AKT1) could phosphorylate threonine residue 606 (T606) within the RSSTIP motif of Kaiso in the cytoplasm. The T606‐phosphorylated Kaiso (pT606‐Kaiso) could directly bind to 14‐3‐3 family proteins, and depletion of T606 phosphorylation by T606A mutation abolished most of the Kaiso–14‐3‐3 binding. In addition, the Kaiso–P120ctn interaction was essential for pT606‐Kaiso accumulation in the cytoplasm. Notably, enforced stratifin (14‐3‐3σ; SFN) overexpression could increase pT606‐Kaiso accumulation in the cytoplasm and de‐repress the transcription of Kaiso target gene cadherin 1 (CDH1), which is a tumour suppressor. Decreased amounts of both pT606‐Kaiso and CDH1 proteins were frequently observed in human gastric cancer tissues compared to paired normal controls. The mRNA levels of 14‐3‐3σ and Kaiso target gene CDH1 showed highly significant positive correlations in both human normal tissues and cancer cell lines by bioinformatics analyses. Furthermore, Kaiso T606A mutant (unable to be phosphorylated) significantly increased the migration and invasion of cancer cells in vitro and promoted the growth of these cells in vivo. In conclusion, Kaiso could be phosphorylated at T606 by AKT1 and pT606‐Kaiso accumulates in the cytoplasm through binding to 14‐3‐3/P120ctn, which de‐represses the Kaiso target gene CDH1 in normal tissues. Decreased Kaiso phosphorylation might contribute to the development of gastrointestinal cancer. The status of Kaiso phosphorylation is a determinant factor for the role of Kaiso in the development of cancer.

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Wnt controls the transcriptional activity of Kaiso through CK1ε-dependent phosphorylation of p120-catenin

Cited by 49 publications

References 33 publications

Rac1 activation upon Wnt stimulation requires Rac1 and Vav2 binding to p120-catenin

Rac1 activation upon Wnt stimulation requires Rac1 and Vav2 binding to p120-catenin

DNA Methylation in Mammalian and Non-Mammalian Organisms

Kaiso phosphorylation at threonine 606 leads to its accumulation in the cytoplasm, reducing its transcriptional repression of the tumour suppressor CDH1

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