Dupre-Crochet, S., Figueroa, A., Hogan, Catherine ![]() |
Abstract
Cadherins are the most crucial membrane proteins for the formation of tight and compact cell-cell contacts. Cadherin-based cell-cell adhesions are dynamically established and/or disrupted during various physiological and pathological processes. However, the molecular mechanisms that regulate cell-cell contacts are not fully understood. In this paper, we report a novel functional role of casein kinase 1 (CK1) in the regulation of cell-cell contacts. Firstly, we observed that IC261, a specific inhibitor of CK1, stabilizes cadherin-based cell-cell contacts, whereas the overexpression of CK1 disrupts them. CK1 colocalizes with E-cadherin and phosphorylates the cytoplasmic domain of E-cadherin in vitro and in a cell culture system. We show that the major CK1 phosphorylation site of E-cadherin is serine 846, a highly conserved residue between classical cadherins. Constitutively phosphorylated E-cadherin (S846D) is unable to localize at cell-cell contacts and has decreased adhesive activity. Furthermore, phosphorylated E-cadherin (S846D) has weaker interactions with β-catenin and is internalized more efficiently than wild-type E-cadherin. These data indicate that CK1 is a novel negative regulator of cadherin-based cell-cell contacts.
Item Type: | Article |
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Date Type: | Publication |
Status: | Published |
Schools: | Biosciences European Cancer Stem Cell Research Institute (ECSCRI) |
Publisher: | American Society for Microbiology |
ISSN: | 0270-7306 |
Last Modified: | 27 Oct 2022 08:46 |
URI: | https://orca.cardiff.ac.uk/id/eprint/63368 |
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