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Aurora A drives early signalling and vesicle dynamics during T-cell activation

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) durin...

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Autores principales: Blas-Rus, Noelia, Bustos-Morán, Eugenio, Pérez de Castro, Ignacio, de Cárcer, Guillermo, Borroto, Aldo, Camafeita, Emilio, Jorge, Inmaculada, Vázquez, Jesús, Alarcón, Balbino, Malumbres, Marcos, Martín-Cófreces, Noa B., Sánchez-Madrid, Francisco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4838898/
https://www.ncbi.nlm.nih.gov/pubmed/27091106
http://dx.doi.org/10.1038/ncomms11389
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author Blas-Rus, Noelia
Bustos-Morán, Eugenio
Pérez de Castro, Ignacio
de Cárcer, Guillermo
Borroto, Aldo
Camafeita, Emilio
Jorge, Inmaculada
Vázquez, Jesús
Alarcón, Balbino
Malumbres, Marcos
Martín-Cófreces, Noa B.
Sánchez-Madrid, Francisco
author_facet Blas-Rus, Noelia
Bustos-Morán, Eugenio
Pérez de Castro, Ignacio
de Cárcer, Guillermo
Borroto, Aldo
Camafeita, Emilio
Jorge, Inmaculada
Vázquez, Jesús
Alarcón, Balbino
Malumbres, Marcos
Martín-Cófreces, Noa B.
Sánchez-Madrid, Francisco
author_sort Blas-Rus, Noelia
collection PubMed
description 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 CD3ζ-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.
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spelling pubmed-48388982016-05-04 Aurora A drives early signalling and vesicle dynamics during T-cell activation Blas-Rus, Noelia Bustos-Morán, Eugenio Pérez de Castro, Ignacio de Cárcer, Guillermo Borroto, Aldo Camafeita, Emilio Jorge, Inmaculada Vázquez, Jesús Alarcón, Balbino Malumbres, Marcos Martín-Cófreces, Noa B. Sánchez-Madrid, Francisco Nat Commun Article 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 CD3ζ-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. Nature Publishing Group 2016-04-19 /pmc/articles/PMC4838898/ /pubmed/27091106 http://dx.doi.org/10.1038/ncomms11389 Text en Copyright © 2016, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Blas-Rus, Noelia
Bustos-Morán, Eugenio
Pérez de Castro, Ignacio
de Cárcer, Guillermo
Borroto, Aldo
Camafeita, Emilio
Jorge, Inmaculada
Vázquez, Jesús
Alarcón, Balbino
Malumbres, Marcos
Martín-Cófreces, Noa B.
Sánchez-Madrid, Francisco
Aurora A drives early signalling and vesicle dynamics during T-cell activation
title Aurora A drives early signalling and vesicle dynamics during T-cell activation
title_full Aurora A drives early signalling and vesicle dynamics during T-cell activation
title_fullStr Aurora A drives early signalling and vesicle dynamics during T-cell activation
title_full_unstemmed Aurora A drives early signalling and vesicle dynamics during T-cell activation
title_short Aurora A drives early signalling and vesicle dynamics during T-cell activation
title_sort aurora a drives early signalling and vesicle dynamics during t-cell activation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4838898/
https://www.ncbi.nlm.nih.gov/pubmed/27091106
http://dx.doi.org/10.1038/ncomms11389
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