- view fewer
Casein kinase 1 is a novel negative regulator of E-cadherin-based cell-cell contacts.
Mol Cell Biol
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 beta-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.
|Title:||Casein kinase 1 is a novel negative regulator of E-cadherin-based cell-cell contacts.|
|Keywords:||Amino Acid Sequence, Animals, Cadherins, Casein Kinase I, Cell Adhesion, Cells, Cultured, Endocytosis, Humans, Indoles, Intercellular Junctions, Isoenzymes, Molecular Sequence Data, Phloroglucinol, Phosphorylation, RNA Interference, Sequence Alignment, Serine, beta Catenin|
|UCL classification:||UCL > School of Life and Medical Sciences
UCL > School of Life and Medical Sciences > Faculty of Life Sciences
Archive Staff Only