Calmodulin‐dependent protein kinase IV regulates nuclear export of Cabin1 during T‐cell activation

Calcium signaling is critical for activation of T lymphocytes and has been proposed to be transduced through multiple calmodulin target proteins. Whereas the calcineurin–NFAT signaling module is critical for all mammalian T cells, the role of calmodulin‐dependent kinase IV (CaMKIV) in mouse naïve CD4 + T‐cell activation remains enigmatic. We have applied lentivius‐mediated RNA interference of CaMKIV to human T cells and found that knockdown of CaMKIV abrogates T‐cell receptor‐mediated transcription of the IL‐2 gene. We demonstrate that CaMKIV directly phosphorylates Cabin1, a transcriptional corepressor for myocyte enhancer factor 2, creating a docking site for 14‐3‐3, which causes its nuclear export. CaMKIV‐mediated nuclear export of Cabin1 is likely to account for a significant part of the requirement of CaMKIV during human T‐cell activation.