First Author | Blas-Rus N | Year | 2016 |
Journal | Nat Commun | Volume | 7 |
Pages | 11389 | PubMed ID | 27091106 |
Mgi Jnum | J:236886 | Mgi Id | MGI:5810042 |
Doi | 10.1038/ncomms11389 | Citation | Blas-Rus N, et al. (2016) Aurora A drives early signalling and vesicle dynamics during T-cell activation. Nat Commun 7:11389 |
abstractText | 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 CD3zeta-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. |