title: Aurora A drives early signalling and vesicle dynamics during T-cell activation.
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.
authors.affiliation: 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.
authors.forename: Noelia
authors.initials: N
authors.lastname: Blas-Rus
authors.affiliation: Cell-cell Communication Laboratory, Vascular Pathophysiology Area, Centro Nacional Investigaciones Cardiovasculares (CNIC), C/ Melchor Fdz Almagro 3, Madrid 28029, Spain.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Bustos-Morán
authors.affiliation: Cell Division and Cancer Group, Centro Nacional de Investigaciones Oncológicas (CNIO), C/ Melchor Fdz Almagro 3, Madrid 28029, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Pérez de Castro
authors.affiliation: Cell Division and Cancer Group, Centro Nacional de Investigaciones Oncológicas (CNIO), C/ Melchor Fdz Almagro 3, Madrid 28029, Spain.
authors.forename: Guillermo
authors.initials: G
authors.lastname: de Cárcer
authors.affiliation: Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, C/ Nicolás cabrera 1, Madrid 28049, Spain.
authors.forename: Aldo
authors.initials: A
authors.lastname: Borroto
authors.affiliation: Laboratory of Cardiovascular Proteomics, Centro Nacional Investigaciones Cardiovasculares (CNIC), C/ Melchor Fdz Almagro 3, Madrid 28029, Spain.
authors.forename: Emilio
authors.initials: E
authors.lastname: Camafeita
authors.affiliation: Laboratory of Cardiovascular Proteomics, Centro Nacional Investigaciones Cardiovasculares (CNIC), C/ Melchor Fdz Almagro 3, Madrid 28029, Spain.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Jorge
authors.affiliation: Laboratory of Cardiovascular Proteomics, Centro Nacional Investigaciones Cardiovasculares (CNIC), C/ Melchor Fdz Almagro 3, Madrid 28029, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Vázquez
authors.affiliation: Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, C/ Nicolás cabrera 1, Madrid 28049, Spain.
authors.forename: Balbino
authors.initials: B
authors.lastname: Alarcón
authors.affiliation: Cell Division and Cancer Group, Centro Nacional de Investigaciones Oncológicas (CNIO), C/ Melchor Fdz Almagro 3, Madrid 28029, Spain.
authors.forename: Marcos
authors.identifier: http://orcid.org/0000-0002-0829-6315
authors.initials: M
authors.lastname: Malumbres
authors.affiliation: 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.|Cell-cell Communication Laboratory, Vascular Pathophysiology Area, Centro Nacional Investigaciones Cardiovasculares (CNIC), C/ Melchor Fdz Almagro 3, Madrid 28029, Spain.
authors.forename: Noa B
authors.initials: NB
authors.lastname: Martín-Cófreces
authors.affiliation: 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.|Cell-cell Communication Laboratory, Vascular Pathophysiology Area, Centro Nacional Investigaciones Cardiovasculares (CNIC), C/ Melchor Fdz Almagro 3, Madrid 28029, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Sánchez-Madrid
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D064096:Aurora Kinase A / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology; D001381:Azepines / Q000494:pharmacology; D017252:CD3 Complex / Q000235:genetics / Q000276:immunology; D022162:Cytoplasmic Vesicles / Q000187:drug effects / Q000276:immunology* / Q000648:ultrastructure; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D054992:Immunological Synapses / Q000187:drug effects / Q000235:genetics; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics / Q000276:immunology; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000235:genetics*; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000235:genetics* / Q000276:immunology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008870:Microtubules / Q000187:drug effects / Q000276:immunology / Q000648:ultrastructure; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000648:ultrastructure; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D064096:Aurora Kinase A; D001381:Azepines; D017252:CD3 Complex; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D037181:Lectins, C-Type; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011948:Receptors, Antigen, T-Cell; D000099192:CD69 Antigens; C121704:CD3 antigen, zeta chain; C508017:IL2RA protein, human; C550258:MLN 8237; C576917:AURKA protein, human