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

Fan Pan1, Anthony R Means, Jun O Liu

  • 1Department of Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

The EMBO Journal
|May 20, 2005
PubMed

Insights

Calmodulin-dependent kinase IV (CaMKIV) is essential for T-cell activation. Blocking CaMKIV stops T-cell receptor signaling and IL-2 gene transcription in human T cells.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Signaling

Background:

  • Calcium signaling is vital for T lymphocyte activation.
  • The calcineurin-NFAT pathway is crucial, but the role of calmodulin-dependent kinase IV (CaMKIV) in T-cell activation is unclear.
  • CaMKIV's function in naive CD4+ T-cell activation requires further elucidation.

Purpose of the Study:

  • To investigate the role of CaMKIV in human T-cell activation.
  • To determine the downstream targets and mechanisms of CaMKIV in T-cell signaling.
  • To understand CaMKIV's contribution to T-cell receptor-mediated gene transcription.

Main Methods:

  • Lentivirus-mediated RNA interference (RNAi) was used to knock down CaMKIV in human T cells.
  • T-cell receptor-mediated transcription of the IL-2 gene was analyzed.
  • CaMKIV's direct phosphorylation of Cabin1 and subsequent protein interactions were examined.

Main Results:

  • CaMKIV knockdown abrogated T-cell receptor-mediated IL-2 gene transcription.
  • CaMKIV was shown to directly phosphorylate Cabin1, a transcriptional corepressor.
  • Phosphorylation of Cabin1 by CaMKIV creates a 14-3-3 binding site, leading to its nuclear export.

Conclusions:

  • CaMKIV plays a critical role in human T-cell activation.
  • CaMKIV-mediated phosphorylation and nuclear export of Cabin1 contribute significantly to T-cell activation.
  • This study elucidates a novel mechanism of CaMKIV action in T-cell signaling.

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