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dc.contributor.authorBlas-Rus, Noelia 
dc.contributor.authorBustos-Moran, Eugenio 
dc.contributor.authorPérez de Castro, Ignacio 
dc.contributor.authorde Carcer Diez, Guillermo 
dc.contributor.authorBorroto, Aldo
dc.contributor.authorCamafeita, Emilio 
dc.contributor.authorJorge, Inmaculada 
dc.contributor.authorVazquez, Jesus 
dc.contributor.authorAlarcón, Balbino
dc.contributor.authorMalumbres Martinez, Marcos 
dc.contributor.authorMartin-Cofreces, Noa B. 
dc.contributor.authorSanchez-Madrid, Francisco 
dc.date.accessioned2017-10-30T13:32:26Z
dc.date.available2017-10-30T13:32:26Z
dc.date.issued2016
dc.identifierISI:000374294400001
dc.identifier.citationNat Commun. 2016; 7:11389
dc.identifier.issn2041-1723
dc.identifier.urihttp://hdl.handle.net/20.500.12105/5241
dc.description.abstractAurora A is a serine/threonine kinase that contributes to the progression of mitosis by inducing microtubule nucleation. Here we have identified an unexpected role for Aurora A kinase in antigen-driven T-cell activation. We find that Aurora A is phosphorylated at the immunological synapse (IS) during TCR-driven cell contact. Inhibition of Aurora A with pharmacological agents or genetic deletion in human or mouse T cells severely disrupts the dynamics of microtubules and CD3z-bearing vesicles at the IS. The absence of Aurora A activity also impairs the activation of early signalling molecules downstream of the TCR and the expression of IL-2, CD25 and CD69. Aurora A inhibition causes delocalized clustering of Lck at the IS and decreases phosphorylation levels of tyrosine kinase Lck, thus indicating Aurora A is required for maintaining Lck active. These findings implicate Aurora A in the propagation of the TCR activation signal.
dc.description.sponsorshipWe thank S. Bartlett for English editing and critical reading of the manuscript, Dr A. Akhmanova for providing reagents, Maria Navarro for the her critical reading of the manuscript and scientific recommendations, Miguel Vicente-Manzanares for his critical reading of the manuscript, and Aitana Sanguino and Maria Jose Lopez for the technical support. We also thank the Confocal Microscopy \& Dynamic Imaging Unit (CNIC), Madrid, Spain. This study was supported by grants SAF2011-25834, SAF2014-55579-R and BIO2012-37926 from the Spanish Ministry of Economy and Competitiveness, INDISNET-S2011/BMD-2332 from the Comunidad de Madrid ERC-2011-AdG 294340-GENTRIS and ERC-2013-AdG 334763-NOVARIPP. Red Cardiovascular RD 12-0042-0056 from Instituto Salud Carlos III (ISCIII). The Centro Nacional de Investigaciones Cardiovasculares (CNIC, Spain) is supported by the Spanish Ministry of Science and Innovation, and the Pro-CNIC Foundation.
dc.language.isoeng
dc.publisherNATURE PUBLISHING GROUP
dc.relation.isversionofPublisher's version
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectIMMUNOLOGICAL SYNAPSE
dc.subjectIMMUNE SYNAPSE
dc.subjectTIRF MICROSCOPY
dc.subjectCENTROSOME MATURATION
dc.subjectANTIGEN RECEPTOR
dc.subjectTYROSINE KINASE
dc.subjectA KINASE
dc.subjectIN-VIVO
dc.subjectLCK
dc.subjectACTIN
dc.titleAurora A drives early signalling and vesicle dynamics during T-cell activation
dc.typeArtículo
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID27091106
dc.format.volume7
dc.identifier.doi10.1038/ncomms11389
dc.contributor.funderMinisterio de Economía y Competitividad (España)
dc.contributor.funderComunidad de Madrid
dc.contributor.funderEC-European Commission
dc.contributor.funderFundación ProCNIC
dc.contributor.funderEuropean Research Council
dc.description.peerreviewed
dc.relation.publisherversionhttps://doi.org/10.1038/ncomms11389
dc.identifier.journalNature Communications
dc.repisalud.centroCNIO
dc.repisalud.orgCNICCNIC::Grupos de investigación::Comunicación Intercelular en la Respuesta Inflamatoria
dc.repisalud.orgCNICCNIC::Grupos de investigación::Proteómica cardiovascular
dc.repisalud.orgCNICCNIC::Unidades técnicas::Proteómica / Metabolómica
dc.repisalud.institucionCNIC
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2014-55579-Res_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7/294340es_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


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