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Unconventional EGF-induced ERK1/2-mediated Kv1.3 endocytosis

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dc.contributor.author Martínez-Mármol, Ramón
dc.contributor.author Comes, Núria
dc.contributor.author Styrczewska, Katarzyna
dc.contributor.author Pérez Verdaguer, Mireia
dc.contributor.author Vicente García, Rubén, 1978-
dc.contributor.author Pujadas, Lluís
dc.contributor.author Soriano, Eduardo
dc.contributor.author Sorkin, Alexander
dc.contributor.author Felipe, Antonio
dc.date.accessioned 2018-12-05T08:33:09Z
dc.date.available 2018-12-05T08:33:09Z
dc.date.issued 2016
dc.identifier.citation Martínez-Mármol R, Comes N, Styrczewska K, Pérez-Verdaguer M, Vicente R, Pujadas L et al. Unconventional EGF-induced ERK1/2-mediated Kv1.3 endocytosis. Cell Mol Life Sci. 2016 Apr;73(7):1515-28. DOI: 10.1007/s00018-015-2082-0
dc.identifier.issn 1420-682X
dc.identifier.uri http://hdl.handle.net/10230/35988
dc.description.abstract The potassium channel Kv1.3 plays roles in immunity, neuronal development and sensory discrimination. Regulation of Kv1.3 by kinase signaling has been studied. In this context, EGF binds to specific receptors (EGFR) and triggers tyrosine kinase-dependent signaling, which down-regulates Kv1.3 currents. We show that Kv1.3 undergoes EGF-dependent endocytosis. This EGF-mediated mechanism is relevant because is involved in adult neural stem cell fate determination. We demonstrated that changes in Kv1.3 subcellular distribution upon EGFR activation were due to Kv1.3 clathrin-dependent endocytosis, which targets the Kv1.3 channels to the lysosomal degradative pathway. Interestingly, our results further revealed that relevant tyrosines and other interacting motifs, such as PDZ and SH3 domains, were not involved in the EGF-dependent Kv1.3 internalization. However, a new, and yet undescribed mechanism, of ERK1/2-mediated threonine phosphorylation is crucial for the EGF-mediated Kv1.3 endocytosis. Our results demonstrate that EGF triggers the down-regulation of Kv1.3 activity and its expression at the cell surface, which is important for the development and migration of adult neural progenitors.
dc.description.sponsorship Supported by the Ministerio de Economía y Competitividad (MINECO), Spain (BFU2014-54928-R and CSD2008-00005 to AF; SAF2013-42445-R to ES). MPV and KS hold fellowships from the MINECO. RMM and NC were supported by the Juan de la Cierva program (MINECO). AS was supported by NIH grants DA014204 and CA089151
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Springer
dc.relation.ispartof Cellular and Molecular Life Sciences. 2016 Apr;73(7):1515-28
dc.rights © Springer The final publication is available at Springer via http://dx.doi.org/10.1007/s00018-015-2082-0
dc.subject.other Endocitosi
dc.subject.other Factor de creixement epidèrmic
dc.subject.other Farmacologia
dc.subject.other Canals de potassi
dc.subject.other Proteïnes quinases activades per mitògens
dc.title Unconventional EGF-induced ERK1/2-mediated Kv1.3 endocytosis
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1007/s00018-015-2082-0
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2014-54928-R
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/CSD2008-00005
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2013-42445-R
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/acceptedVersion


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