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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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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. |
format | Online Article Text |
id | pubmed-4838898 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
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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