Casein Kinase 1 Is a Novel Negative Regulator of E-Cadherin-Based Cell-Cell Contacts

Dupre-Crochet, Sophie; Figueroa, Angélica; Hogan, Catherine; Ferber, Emma C.; Bialucha, Carl U.; Adams, Joanna M.; Richardson, Emily C. N.; Fujita, Yasuyuki

doi:10.1128/mcb.01590-06

Cited by 85 publications

(82 citation statements)

References 40 publications

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“…Two kinases were markedly better recovered in the BL-ZO-1 samples: MARK2 (Fig. 4, third row, left), which is involved in microtubule dynamics, Wnt signaling, and cell polarization (33) and casein kinase 1 ␣ (KC1A; third row middle), which partially colocalizes with E-cadherin in MDCK cells (34). Phosphorylation of E-cadherin by KC1A inhibits its localization to cell contacts, negatively regulating cell adhesion (34).…”

Section: Specific Proteins Are Differentially Tagged In Cells Expressmentioning

confidence: 99%

“…4, third row, left), which is involved in microtubule dynamics, Wnt signaling, and cell polarization (33) and casein kinase 1 ␣ (KC1A; third row middle), which partially colocalizes with E-cadherin in MDCK cells (34). Phosphorylation of E-cadherin by KC1A inhibits its localization to cell contacts, negatively regulating cell adhesion (34). In addition, KC1A can phosphorylate occludin in vitro, but the functional significance of this is unknown (35).…”

Section: Specific Proteins Are Differentially Tagged In Cells Expressmentioning

confidence: 99%

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The N and C Termini of ZO-1 Are Surrounded by Distinct Proteins and Functional Protein Networks

Itallie

Aponte

Tietgens

et al. 2013

Journal of Biological Chemistry

109

118

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Background: Biotin ligase tagging with ZO-1 was applied to identify a more complete tight junction proteome. Results: Identical but also different proteins and functional networks were identified near the N and C ends of ZO-1. Conclusion:The ends of ZO-1 are embedded in different functional subcompartments of the tight junction. Significance: Biotin tagging with ZO-1 expands the tight junction proteome and defines subcompartments of the junction.

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Section: Specific Proteins Are Differentially Tagged In Cells Expressmentioning

confidence: 99%

Section: Specific Proteins Are Differentially Tagged In Cells Expressmentioning

confidence: 99%

The N and C Termini of ZO-1 Are Surrounded by Distinct Proteins and Functional Protein Networks

Itallie

Aponte

Tietgens

et al. 2013

Journal of Biological Chemistry

109

118

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“…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 And mentioning

confidence: 99%

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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“…However, there are conflicting data as to whether CKI activity actually is negative for the ␤-catenin/E-cadherin interaction (11,12). We have previously shown that Wnt-5a activates CKI␣ in human breast epithelial cells (16).…”

Section: Wnt-5a Affects ␤-Catenin/e-cadherinmentioning

confidence: 99%

“…GSK-3␤ 2 and CK2 have been implicated as potential kinases. In contrast, phosphorylation of serine 846 by CKI and tyrosine phosphorylation of both E-cadherin and ␤-catenin has been suggested to decrease the association (10,11), although conflicting data are present (12). Still, there is little evidence concerning ␤-catenin phosphorylation and E-cadherin association.…”

mentioning

confidence: 99%

Wnt-5a-CKIα Signaling Promotes β-Catenin/E-Cadherin Complex Formation and Intercellular Adhesion in Human Breast Epithelial Cells

Medrek

Landberg

Andersson

et al. 2009

Journal of Biological Chemistry

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Wnt-5a is a non-transforming Wnt protein that is implicated in cell polarity, adhesion, and motility. We have previously shown that low expression of Wnt-5a is a predictor of shorter disease-free survival in human breast cancer. Here, we investigated whether ␤-catenin/E-cadherin-mediated cell-cell adhesion was affected by loss of Wnt-5a in breast carcinomas, thereby promoting a metastatic behavior of the tumor. We show that Wnt-5a stimulation of human breast epithelial cells leads to an increased Ca 2؉ -dependent cell-cell adhesion. Furthermore, Wnt-5a/casein kinase I␣ (CKI␣)-specific Ser-45 phosphorylation of ␤-catenin is associated with an increased complex formation of ␤-catenin/E-cadherin. Mutation of Ser-45 decreases the ␤-catenin/E-cadherin association. Also, the inhibitory effect of Wnt-5a on breast epithelial cell invasion is reduced upon mutation of ␤-catenin-Ser-45. The Wnt-5a-CKI␣-induced Ser-45 phosphorylation does not lead to degradation of ␤-catenin. Finally we show that human breast cancers lacking Wnt-5a protein have a significantly lower level of membrane-associated ␤-catenin. Down-regulation of Wnt-5a expression and subsequent reduction of membrane-associated ␤-catenin in invasive breast cancer, can therefore contribute to a decreased cell-cell adhesion and increased motility resulting in a higher probability for metastatic disease.In a normal mammary gland the ducts are lined with epithelial cells that are both interconnected and connected to the basement membrane. Mutations in genes encoding adhesion molecules have been implicated in the progression of breast cancer (1). E-cadherin is a transmembrane, calcium (Ca 2ϩ )-dependent adhesion molecule that connects adjacent epithelial cells. The loss of cell-cell adhesion at the original tumor site has been suggested to be related to the loss of E-cadherin expression or function in many epithelial cancers (2). The E-cadherins are dynamically linked to the cytoskeleton via ␤-catenin, plakoglobin, p120, and ␣-catenin (3, 4). Mutations in the E-cadherin gene are frequent in invasive lobular breast cancers, whereas they are absent or might occur at a low frequency in the more common invasive ductal breast carcinomas (5). Despite this, a low membrane expression of ␤-catenin was recently shown to be associated with a poor outcome in human breast cancer patients (6). The question as to whether Wnt ␤-catenin signaling can affect E-cadherin-dependent cellular adhesion, or vice versa, has long been debated (7).␤-Catenin plays a role both in the ␤-catenin/E-cadherin complex and as a transcriptional regulator in the nucleus upon canonical Wnt signaling (reviewed in Ref. 8). There are therefore three different pools of ␤-catenin; a membrane bound, a cytoplasmic that is constantly being phosphorylated and targeted for ubiquitination and degradation, and a nuclear unphosphorylated form. It has previously been suggested that ␤-catenin targeted to adhesive or transcriptional complexes have distinct molecular forms that would allow it to coordinate the two processes...

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Casein Kinase 1 Is a Novel Negative Regulator of E-Cadherin-Based Cell-Cell Contacts

Cited by 85 publications

References 40 publications

The N and C Termini of ZO-1 Are Surrounded by Distinct Proteins and Functional Protein Networks

The N and C Termini of ZO-1 Are Surrounded by Distinct Proteins and Functional Protein Networks

Wnt/beta-Catenin Signaling and Small Molecule Inhibitors

Wnt-5a-CKIα Signaling Promotes β-Catenin/E-Cadherin Complex Formation and Intercellular Adhesion in Human Breast Epithelial Cells

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