Aurora A drives early signalling and vesicle dynamics during T-cell activation
Entity
UAM. Departamento de Medicina; Centro de Biología Molecular Severo Ochoa (CBM)Publisher
Nature Publishing GroupDate
2016-04-19Citation
10.1038/ncomms11389
Nature Communications 7 (2016): 11389
ISSN
2041-1723DOI
10.1038/ncomms11389Funded by
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 FoundationProject
Gobierno de España. SAF2011-25834; Gobierno de España. SAF2014-55579-R; Gobierno de España. BIO2012-37926; Comunidad de Madrid. S2011/BMD-2332/INDISNET; info:eu-repo/grantAgreement/EC/FP7/102247; info:eu-repo/grantAgreement/EC/FP7/334763Editor's Version
http://dx.doi.org/10.1038/ncomms11389 |www.nature.com/naturecommunicationsSubjects
Autophosphorylation; CD4+ T lymphocyte; Human cell; Immunoprecipitation; MedicinaAbstract
Aurora 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
Files in this item
Google Scholar:Blas-Rus, Noelia
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Bustos-Morán, Eugenio
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Pérez de Castro, Ignacio
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Cárcer, Guillermo de
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Borroto, Aldo
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Camafeita, Emilio
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Jorge, Inmaculada
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Vázquez, Jesús
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Alarcón, Baslbino
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Malumbres, Marcos
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Martín-Cófreces, Noa
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Sánchez Madrid, Francisco
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