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Molecular and Cellular Biology, May 2007, p. 3804-3816, Vol. 27, No. 10
0270-7306/07/$08.00+0     doi:10.1128/MCB.01590-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Casein Kinase 1 Is a Novel Negative Regulator of E-Cadherin-Based Cell-Cell Contacts{triangledown} ,{dagger}

Sophie Dupre-Crochet ,{ddagger},§ Angélica Figueroa,§ Catherine Hogan, Emma C. Ferber, Carl Uli Bialucha, Joanna Adams, Emily C. N. Richardson, and Yasuyuki Fujita*

MRC Laboratory for Molecular Cell Biology and Cell Biology Unit and Department of Biology, University College London, Gower Street, London WC1E 6BT, United Kingdom

Received 25 August 2006/ Returned for modification 3 October 2006/ Accepted 26 February 2007

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 ß-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.


* Corresponding author. Mailing address: MRC Laboratory for Molecular Cell Biology and Cell Biology Unit and Department of Biology, University College London, Gower Street, London WC1E 6BT, United Kingdom. Phone: 44-20-7679-7208. Fax: 44-20-7679-7805. E-mail: y.fujita{at}ucl.ac.uk

{triangledown} Published ahead of print on 12 March 2007.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

{ddagger} Present address: INSERM UMR 757, Université Paris-Sud, Bat 443, 91405 Orsay Cedex, France.

§ S.D.-C. and A.F. contributed equally to this work.


Molecular and Cellular Biology, May 2007, p. 3804-3816, Vol. 27, No. 10
0270-7306/07/$08.00+0     doi:10.1128/MCB.01590-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.




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