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Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c
07:42

Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c

Published on: June 29, 2011

Role of mitogen-activated protein kinases in activation-induced apoptosis of T cells

L Zhu1, X Yu, Y Akatsuka

  • 1Human Immunogenetics Program, Division of Clinical Research, Fred Hutc hinson Cancer Research Center, Seattle, WA 98104, USA.

Immunology
|August 14, 1999
PubMed

Insights

Extracellular signal-regulated kinase (ERK) activation is crucial for T-cell apoptosis, driving Fas ligand expression during activation-induced cell death (AICD). Jun N-terminal kinase (JNK) activation alone is insufficient for this process.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Mitogen-activated protein (MAP) kinases, including Jun N-terminal kinase (JNK), regulate apoptosis.
  • Activation-induced cell death (AICD) is T-cell apoptosis triggered by T-cell receptor (TCR) restimulation.

Purpose of the Study:

  • Investigate the role of extracellular signal-regulated protein kinase (ERK), another MAP kinase, in T-cell AICD.
  • Determine if ERK activation is necessary for AICD and its relationship with JNK activation and Fas ligand (FasL) expression.

Main Methods:

  • Studied JNK and ERK activation kinetics upon TCR ligation in T cells.
  • Utilized a chemical inhibitor (PD 098059) to block ERK activation.
  • Assessed FasL expression and apoptosis induction via TCR cross-linking and anti-Fas antibody treatment.

Main Results:

  • Both JNK and ERK were rapidly activated following TCR ligation before AICD onset.
  • PD 098059 inhibited ERK activation and subsequent apoptosis, but not JNK activation.
  • TCR cross-linking induced FasL expression, correlating with ERK activation.
  • Direct Fas receptor ligation induced apoptosis independently of ERK activation and PD 098059 treatment.

Conclusions:

  • ERK activation is an early event in TCR-induced T-cell apoptosis, essential for FasL expression.
  • JNK activation alone is insufficient to induce AICD.
  • ERK's role appears to be in mediating FasL induction rather than apoptosis directly.

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