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.
Duke Scholars
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Related Subject Headings
- Transcription, Genetic
- Transcription Factors
- T-Lymphocytes
- Receptors, Antigen, T-Cell
- Protein Transport
- Phosphorylation
- Phosphoproteins
- Myogenic Regulatory Factors
- MEF2 Transcription Factors
- Lymphocyte Activation
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Transcription, Genetic
- Transcription Factors
- T-Lymphocytes
- Receptors, Antigen, T-Cell
- Protein Transport
- Phosphorylation
- Phosphoproteins
- Myogenic Regulatory Factors
- MEF2 Transcription Factors
- Lymphocyte Activation