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

Fan Pan, Anthony R. Means, Jun O. Liu

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2104-2113
Number of pages10
JournalEMBO Journal
Volume24
Issue number12
DOIs
StatePublished - Jun 15 2005

    Fingerprint

Keywords

  • CaMKIV
  • Cabin1
  • Calcium
  • MEF2
  • T-cell activation

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this