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Nuclear factor of activated T cells c is a target of p38 mitogen-activated protein kinase in T cells

Chia-Cheng Wu1, Shu-Ching Hsu, Hsiu-Ming Shih

  • 1Graduate Institute of Immunology, School of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China.

Molecular and Cellular Biology
|August 29, 2003
PubMed

Insights

p38 mitogen-activated protein kinase (MAPK) directly targets nuclear factor of activated T cells (NFAT) in T-cell activation. p38 MAPK promotes NFAT activation through multiple stages, ultimately driving T-cell responses.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Signaling

Background:

  • p38 mitogen-activated protein kinase (MAPK) plays a crucial role in T-cell activation.
  • Nuclear factor of activated T cells (NFAT) is a key transcription factor involved in T-cell function.

Purpose of the Study:

  • To investigate the direct relationship between p38 MAPK and NFAT activation in T cells.
  • To elucidate the specific mechanisms by which p38 MAPK influences NFAT activity.

Main Methods:

  • Inhibition of p38 MAPK activity in T cells.
  • Analysis of NFAT promoter activity and mRNA levels.
  • Assessment of mRNA stability and translation.
  • Investigation of NFAT interaction with coactivators and nuclear localization.

Main Results:

  • p38 MAPK directly targets and selectively inactivates NFAT upon inhibition.
  • p38 MAPK activates NFAT promoter, enhances NFAT mRNA transcription, stability, and translation.
  • p38 MAPK promotes NFAT interaction with CREB-binding protein.
  • p38 MAPK also moderately enhances NFAT nuclear expulsion, indicating opposing effects.

Conclusions:

  • p38 MAPK is a critical regulator of NFAT activation in T cells.
  • The overall effect of p38 MAPK on NFAT in T cells is activation, despite some opposing effects on specific stages.
  • Understanding this pathway is vital for T-cell immunology research.

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