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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • 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
  • Phosphorylation
  • Protein Kinase Inhibitors / pharmacology
  • Pyrimidines / pharmacology
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology
  • Signal Transduction / immunology*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / ultrastructure

Substances

  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • Azepines
  • CD3 Complex
  • CD3 antigen, zeta chain
  • CD69 antigen
  • IL2RA protein, human
  • Interleukin-2
  • Interleukin-2 Receptor alpha Subunit
  • Lectins, C-Type
  • MLN 8237
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Receptors, Antigen, T-Cell
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
  • AURKA protein, human
  • Aurora Kinase A