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ERK5 is involved in TCR-induced apoptosis through the modification of Nur77

Yasushi Fujii1, Satoshi Matsuda, Gensuke Takayama

  • 1Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.

Genes to Cells : Devoted to Molecular & Cellular Mechanisms
|April 24, 2008
PubMed

Insights

The mitogen-activated protein kinase (MAPK) ERK5 phosphorylates the nuclear receptor Nur77, initiating T cell apoptosis. This phosphorylation is crucial for T cell receptor-mediated cell death during T cell activation.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Signaling

Background:

  • Nur77, a nuclear orphan steroid receptor, induces apoptosis in thymocytes and T cell lines.
  • Nur77's function is regulated by post-translational modifications.
  • T cell activation involves T cell receptor (TCR) signaling and negative selection.

Purpose of the Study:

  • To investigate the role of MAPK-induced phosphorylation of Nur77 in T cell apoptosis.
  • To identify specific MAPK pathways involved in Nur77 regulation during T cell activation.

Main Methods:

  • Stimulation of T cells and T cell lines via T cell receptor (TCR).
  • Analysis of Nur77 phosphorylation by MAPK pathways, including ERK5 and ERK2.
  • Assessment of Nur77 transcriptional activity and its role in apoptosis.
  • Inhibition of signaling pathways to evaluate effects on TCR-induced cell death.

Main Results:

  • ERK5 (big MAP kinase 1, BMK1) phosphorylates Nur77 upon TCR stimulation, leading to its transcriptional activation.
  • ERK2 also phosphorylates Nur77 but does not activate its transcriptional function.
  • Blocking the ERK5 signaling pathway significantly suppressed TCR-induced T cell death.

Conclusions:

  • ERK5-mediated phosphorylation of Nur77 is a critical step in TCR-induced T cell apoptosis.
  • ERK5 acts as a key regulator of Nur77 function and T cell survival pathways.

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