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Calmodulin‐dependent protein kinase IV regulates nuclear export of Cabin1 during T‐cell activation
Author(s) -
Pan Fan,
Means Anthony R,
Liu Jun O
Publication year - 2005
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600685
Subject(s) - biology , calmodulin , protein kinase a , nuclear protein , microbiology and biotechnology , nuclear export signal , kinase , cell nucleus , biochemistry , enzyme , gene , transcription factor , cytoplasm
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.