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Nat Commun. 2016 Apr 19;7:11389. doi: 10.1038/ncomms11389.

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

Author information

1
Servicio de Inmunología, Hospital Universitario de la Princesa, Instituto Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid, C/ Diego de León 62, Madrid 28006, Spain.
2
Cell-cell Communication Laboratory, Vascular Pathophysiology Area, Centro Nacional Investigaciones Cardiovasculares (CNIC), C/ Melchor Fdz Almagro 3, Madrid 28029, Spain.
3
Cell Division and Cancer Group, Centro Nacional de Investigaciones Oncológicas (CNIO), C/ Melchor Fdz Almagro 3, Madrid 28029, Spain.
4
Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, C/ Nicolás cabrera 1, Madrid 28049, Spain.
5
Laboratory of Cardiovascular Proteomics, Centro Nacional Investigaciones Cardiovasculares (CNIC), C/ Melchor Fdz Almagro 3, Madrid 28029, Spain.

Abstract

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.

PMID:
27091106
PMCID:
PMC4838898
DOI:
10.1038/ncomms11389
[Indexed for MEDLINE]
Free PMC Article

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