Aurora A drives early signalling and vesicle dynamics during T-cell activation.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 27091106.
- Also identified by DOI 10.1038/ncomms11389 and PMC identifier 4838898.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Aurora Kinase A
- Cytoplasmic Vesicles
- Lymphocyte Activation
- Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
- Signal Transduction
- T-Lymphocytes