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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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Detalles Bibliográficos
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
Descripción
Sumario: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.