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 naive 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.
Mesh Terms:
14-3-3 Proteins, Adaptor Proteins, Signal Transducing, Calcineurin, Calcium-Calmodulin-Dependent Protein Kinase Type 4, Calcium-Calmodulin-Dependent Protein Kinases, Calmodulin, Cell Nucleus, DNA-Binding Proteins, Gene Expression Regulation, Humans, Interleukin-2, Ionomycin, Ionophores, Lymphocyte Activation, Myogenic Regulatory Factors, Phosphoproteins, Phosphorylation, Protein Transport, Receptors, Antigen, T-Cell, T-Lymphocytes, Transcription Factors, Transcription, Genetic
EMBO J.
Date: Jun. 15, 2005
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