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

• Published in: Nature communications Vol. 7; no. 1; p. 11389
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 19.04.2016; Nature Publishing Group; Nature Portfolio
• Subjects: 14; 14/1; 14/19; 631/250/1619/554; 631/250/2152/1566/1618; 631/45/275; 631/80/86; 82; 82/29; 82/58; 96; 96/109; 96/35; Animals; Antigens, CD - genetics; Antigens, CD - immunology; Antigens, Differentiation, T-Lymphocyte - genetics; Antigens, Differentiation, T-Lymphocyte - immunology; Aurora Kinase A - antagonists & inhibitors; Aurora Kinase A - genetics; Aurora Kinase A - immunology; Azepines - pharmacology; CD3 Complex - genetics; CD3 Complex - immunology; Cytoplasmic Vesicles - drug effects; Cytoplasmic Vesicles - immunology; Cytoplasmic Vesicles - ultrastructure; Female; Gene Expression Regulation; Humanities and Social Sciences; Humans; Immunological Synapses - drug effects; Immunological Synapses - genetics; Interleukin-2 - genetics; Interleukin-2 - immunology; Interleukin-2 Receptor alpha Subunit - genetics; Interleukin-2 Receptor alpha Subunit - immunology; Lectins, C-Type - genetics; Lectins, C-Type - immunology; Lymphocyte Activation - drug effects; Lymphocyte Activation - genetics; Lymphocyte Specific Protein Tyrosine Kinase p56(lck) - genetics; Lymphocyte Specific Protein Tyrosine Kinase p56(lck) - immunology; Male; Mice; Mice, Transgenic; Microtubules - drug effects; Microtubules - immunology; Microtubules - ultrastructure; multidisciplinary; Phosphorylation; Protein Kinase Inhibitors - pharmacology; Pyrimidines - pharmacology; Receptors, Antigen, T-Cell - genetics; Receptors, Antigen, T-Cell - immunology; Science; Science (multidisciplinary); Signal Transduction - immunology; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; T-Lymphocytes - ultrastructure
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms11389

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. Aurora A is a protein kinase that contributes to the progression of mitosis by stimulating microtubule nucleation. Here the authors show that Aurora A also functions during T cell activation by maintaining TCR signaling through Lck activation.