A p120-catenin-CK1epsilon complex regulates Wnt signaling

p120-catenin is an E-cadherin-associated protein that modulates E-cadherin function and stability. We describe here that p120-catenin is required for Wnt pathway signaling. p120-catenin binds and is phosphorylated by CK1ε in response to Wnt3a. p120-catenin also associates to the Wnt co-receptor LRP5...

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Autores: Casagolda, David, Valle Pérez, Beatriz del, Valls, Gabriela, Lugilde, Ero, Vinyoles, Meritxell, Casado Vela, Juan, Solanas, Guiomar, Batlle Gómez, Eduard, Reynolds, Albert B., Casal, José Ignacio, García de Herreros, Antonio, Duñach, Mireia
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2010
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/25587
Acceso en línea:http://hdl.handle.net/10230/25587
http://dx.doi.org/10.1242/jcs.067512
Access Level:acceso abierto
Palabra clave:Proteïnes quinases -- Metabolisme
Cadherines
CK1
E-cadherin
Wnt
p120-catenin
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spelling A p120-catenin-CK1epsilon complex regulates Wnt signalingCasagolda, DavidValle Pérez, Beatriz delValls, GabrielaLugilde, EroVinyoles, MeritxellCasado Vela, JuanSolanas, GuiomarBatlle Gómez, EduardReynolds, Albert B.Casal, José IgnacioGarcía de Herreros, AntonioDuñach, MireiaProteïnes quinases -- MetabolismeCadherinesCK1E-cadherinWntp120-cateninp120-catenin is an E-cadherin-associated protein that modulates E-cadherin function and stability. We describe here that p120-catenin is required for Wnt pathway signaling. p120-catenin binds and is phosphorylated by CK1ε in response to Wnt3a. p120-catenin also associates to the Wnt co-receptor LRP5/6, an interaction mediated by E-cadherin, showing an unexpected physical link between adherens junctions and a Wnt receptor. Depletion of p120-catenin abolishes CK1ε binding to LRP5/6 and prevents CK1ε activation upon Wnt3a stimulation. Elimination of p120-catenin also inhibits early responses to Wnt, such as LRP5/6 and Dvl-2 phosphorylation and axin recruitment to the signalosome, as well as later effects, such as β-catenin stabilization. Moreover, since CK1ε is also required for E-cadherin phosphorylation, a modification that decreases the affinity for β-catenin, p120-catenin depletion prevents the increase in β-catenin transcriptional activity even in the absence of β-catenin degradation. Therefore, these results demonstrate a novel and crucial function of p120-catenin in Wnt signaling and unveil additional points of regulation by this factor of β-catenin transcriptional activity different of β-catenin stability.This study was supported by grants awarded by the Ministerio de Ciencia e Innovación: BFU2006-03203 and BFU2009-07578 to M.D. and SAF2006-00339 to A.G.H. Partial support from the Instituto Carlos III (RD06/0020/0040) and the Generalitat de Catalunya (2009SGR867 and 2009SGR585) is also appreciated. D.C. and G.V. were supported by predoctoral fellowships from the Ministerio de Educación and E.L., from the UAB.Company of Biologists201620162010info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/25587http://dx.doi.org/10.1242/jcs.067512reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésJournal of cell science. 2010; 123(Pt 15): 2621-2631info:eu-repo/grantAgreement/ES/2PN/BFU2006-03203info:eu-repo/grantAgreement/ES/2PN/SAF2006-00339info:eu-repo/grantAgreement/ES/3PN/BFU2009-07578© Company of Biologists http://jcs.biologists.org/content/joces/123/15/2621.full.pdf DOI 10.1242/jcs.067512info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/255872026-06-12T07:21:37Z
dc.title.none.fl_str_mv A p120-catenin-CK1epsilon complex regulates Wnt signaling
title A p120-catenin-CK1epsilon complex regulates Wnt signaling
spellingShingle A p120-catenin-CK1epsilon complex regulates Wnt signaling
Casagolda, David
Proteïnes quinases -- Metabolisme
Cadherines
CK1
E-cadherin
Wnt
p120-catenin
title_short A p120-catenin-CK1epsilon complex regulates Wnt signaling
title_full A p120-catenin-CK1epsilon complex regulates Wnt signaling
title_fullStr A p120-catenin-CK1epsilon complex regulates Wnt signaling
title_full_unstemmed A p120-catenin-CK1epsilon complex regulates Wnt signaling
title_sort A p120-catenin-CK1epsilon complex regulates Wnt signaling
dc.creator.none.fl_str_mv Casagolda, David
Valle Pérez, Beatriz del
Valls, Gabriela
Lugilde, Ero
Vinyoles, Meritxell
Casado Vela, Juan
Solanas, Guiomar
Batlle Gómez, Eduard
Reynolds, Albert B.
Casal, José Ignacio
García de Herreros, Antonio
Duñach, Mireia
author Casagolda, David
author_facet Casagolda, David
Valle Pérez, Beatriz del
Valls, Gabriela
Lugilde, Ero
Vinyoles, Meritxell
Casado Vela, Juan
Solanas, Guiomar
Batlle Gómez, Eduard
Reynolds, Albert B.
Casal, José Ignacio
García de Herreros, Antonio
Duñach, Mireia
author_role author
author2 Valle Pérez, Beatriz del
Valls, Gabriela
Lugilde, Ero
Vinyoles, Meritxell
Casado Vela, Juan
Solanas, Guiomar
Batlle Gómez, Eduard
Reynolds, Albert B.
Casal, José Ignacio
García de Herreros, Antonio
Duñach, Mireia
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Proteïnes quinases -- Metabolisme
Cadherines
CK1
E-cadherin
Wnt
p120-catenin
topic Proteïnes quinases -- Metabolisme
Cadherines
CK1
E-cadherin
Wnt
p120-catenin
description p120-catenin is an E-cadherin-associated protein that modulates E-cadherin function and stability. We describe here that p120-catenin is required for Wnt pathway signaling. p120-catenin binds and is phosphorylated by CK1ε in response to Wnt3a. p120-catenin also associates to the Wnt co-receptor LRP5/6, an interaction mediated by E-cadherin, showing an unexpected physical link between adherens junctions and a Wnt receptor. Depletion of p120-catenin abolishes CK1ε binding to LRP5/6 and prevents CK1ε activation upon Wnt3a stimulation. Elimination of p120-catenin also inhibits early responses to Wnt, such as LRP5/6 and Dvl-2 phosphorylation and axin recruitment to the signalosome, as well as later effects, such as β-catenin stabilization. Moreover, since CK1ε is also required for E-cadherin phosphorylation, a modification that decreases the affinity for β-catenin, p120-catenin depletion prevents the increase in β-catenin transcriptional activity even in the absence of β-catenin degradation. Therefore, these results demonstrate a novel and crucial function of p120-catenin in Wnt signaling and unveil additional points of regulation by this factor of β-catenin transcriptional activity different of β-catenin stability.
publishDate 2010
dc.date.none.fl_str_mv 2010
2016
2016
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/25587
http://dx.doi.org/10.1242/jcs.067512
url http://hdl.handle.net/10230/25587
http://dx.doi.org/10.1242/jcs.067512
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Journal of cell science. 2010; 123(Pt 15): 2621-2631
info:eu-repo/grantAgreement/ES/2PN/BFU2006-03203
info:eu-repo/grantAgreement/ES/2PN/SAF2006-00339
info:eu-repo/grantAgreement/ES/3PN/BFU2009-07578
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Company of Biologists
publisher.none.fl_str_mv Company of Biologists
dc.source.none.fl_str_mv reponame:Repositorio Digital de la UPF
instname:Universitat Pompeu Fabra
instname_str Universitat Pompeu Fabra
reponame_str Repositorio Digital de la UPF
collection Repositorio Digital de la UPF
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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