dc.contributor.author | Sánchez-Fernández, Guzmán | |
dc.contributor.author | Cabezudo, Sofía | |
dc.contributor.author | García-Hoz, Carlota | |
dc.contributor.author | Tobin, Andrew B. | |
dc.contributor.author | Mayor Menéndez, Federico | |
dc.contributor.author | Ribas Núñez, Catalina | |
dc.contributor.other | UAM. Departamento de Biología Molecular | es_ES |
dc.date.accessioned | 2015-05-06T08:37:10Z | |
dc.date.available | 2015-05-06T08:37:10Z | |
dc.date.issued | 2013-12-17 | |
dc.identifier.citation | Plos One 8.12 (2013): e84174 | es_ES |
dc.identifier.issn | 1932-6203 (online) | es_ES |
dc.identifier.uri | http://hdl.handle.net/10486/665938 | |
dc.description.abstract | G-protein-coupled receptors (GPCRs) are known to activate both G protein- and β-arrestin-dependent signalling cascades. The initiation of mitogen-activated protein kinase (MAPK) pathways is a key downstream event in the control of cellular functions including proliferation, differentiation, migration and apoptosis. Both G proteins and β-arrestins have been reported to mediate context-specific activation of ERK1/2, p38 and JNK MAPKs. Recently, the activation of ERK5 MAPK by Gq-coupled receptors has been described to involve a direct interaction between Gαq and two novel effectors, PKCζ and MEK5. However, the possible contribution of β-arrestin towards this pathway has not yet been addressed. In the present work we sought to investigate the role of receptor internalization processes and β-arrestin recruitment in the activation of ERK5 by Gq-coupled GPCRs. Our results show that ERK5 activation is independent of M1 or M3 muscarinic receptor internalization. Furthermore, we demonstrate that phosphorylation-deficient muscarinic M1 and M3 receptors are still able to fully activate the ERK5 pathway, despite their reported inability to recruit β-arrestins. Indeed, the overexpression of Gαq, but not that of β-arrestin1 or β-arrestin2, was found to potently enhance ERK5 activation by GPCRs, whereas silencing of β-arrestin2 expression did not affect the activation of this pathway. Finally, we show that a β-arrestin-biased mutant form of angiotensin II (SII; Sar1-Ile4-Ile8 AngII) failed to promote ERK5 phosphorylation in primary cardiac fibroblasts, as compared to the natural ligand. Overall, this study shows that the activation of ERK5 MAPK by model Gq-coupled GPCRs does not depend on receptor internalization, β-arrestin recruitment or receptor phosphorylation but rather is dependent on Gαq-signalling | en_US |
dc.description.sponsorship | The study was funded by grants from Ministerio de Educación y Ciencia (SAF2011-23800), Fundación Ramón Areces, The Cardiovascular Diseases Network of Ministerio Sanidad y Consumo-Instituto Carlos III (RD12/0042/0012), Comunidad de Madrid (S-2011/BMD-2332) and Instituto de Salud Carlos III (PI11/00126). | en_US |
dc.format.extent | 8 pag. | en |
dc.format.mimetype | application/pdf | en |
dc.language.iso | eng | en |
dc.publisher | Public Library of Science | en_US |
dc.relation.ispartof | Plos One | en_US |
dc.rights | © 2013 Sánchez-Fernández et al. | en_US |
dc.subject.other | Arrestins | en_US |
dc.subject.other | Enzyme Activation | en_US |
dc.subject.other | Fibroblasts | en_US |
dc.subject.other | GTP-Binding Protein alpha Subunits | en_US |
dc.subject.other | Phosphorylation | en_US |
dc.title | ERK5 activation by Gq-coupled muscarinic receptors is independent of receptor internalization and β-arrestin recruitment | en_US |
dc.type | article | en |
dc.subject.eciencia | Biología y Biomedicina / Biología | es_ES |
dc.identifier.doi | 10.1371/journal.pone.0084174 | es_ES |
dc.identifier.publicationfirstpage | e84174 | es_ES |
dc.identifier.publicationissue | 12 | es_ES |
dc.identifier.publicationlastpage | e84174 | es_ES |
dc.identifier.publicationvolume | 8 | es_ES |
dc.relation.projectID | Comunidad de Madrid. S2010/BMD-2332/INDISNET | es_ES |
dc.type.version | info:eu-repo/semantics/publishedVersion | en |
dc.rights.accessRights | openAccess | en |
dc.authorUAM | Cabezudo Violedo, Sofía (264747) | |
dc.authorUAM | Mayor Menendez, Federico (260516) | |
dc.facultadUAM | Facultad de Ciencias | |
dc.institutoUAM | Centro de Biología Molecular Severo Ochoa (CBMSO) | |
dc.institutoUAM | Instituto de Investigación Sanitaria Hospital Universitario de La Princesa (IIS-Princesa) | |