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MSK regulate TCR-induced CREB phosphorylation but not immediate early gene transcription

Madlen Kaiser1, Giselle R Wiggin, Kurt Lightfoot

  • 1MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, UK.

European Journal of Immunology
|August 3, 2007
PubMed

Insights

Mitogen- and stress-activated kinases (MSK) are activated by T cell receptor (TCR) stimulation. MSK is crucial for T cell proliferation and IL-2 receptor CD25 expression, despite not being essential for T cell development.

Area of Science:

  • Immunology
  • Cell Signaling
  • Molecular Biology

Background:

  • T cell receptor (TCR) stimulation activates ERK1/2 and p38 mitogen-activated protein kinase (MAPK) pathways.
  • Mitogen- and stress-activated kinases (MSK) are downstream effectors of MAPK signaling in various cell types.

Purpose of the Study:

  • To investigate the role of MSK in T cell activation and function following TCR stimulation.
  • To determine if MSK is involved in the phosphorylation of CREB and subsequent gene transcription in T cells.

Main Methods:

  • Utilized MSK1/2-knockout mice and wild-type littermates.
  • Analyzed T cell development, proliferation, and gene expression.
  • Assessed CREB phosphorylation and IL-2 receptor CD25 upregulation in response to TCR stimulation.

Main Results:

  • TCR stimulation activates MSK in T cells.
  • MSK is essential for TCR-induced CREB phosphorylation in naive T cells and T lymphoblasts.
  • MSK1/2-knockout mice exhibit reduced T cell numbers in spleens and impaired IL-2-induced proliferation.
  • TCR-induced upregulation of CD25 and IL-2-induced CREB phosphorylation are reduced in MSK-deficient T cells.

Conclusions:

  • MSK plays a critical role in T cell proliferation and IL-2 receptor expression post-TCR stimulation.
  • While not essential for T cell development, MSK is required for specific aspects of T cell function, including IL-2 signaling.
  • MSK is a key mediator of TCR-induced CREB phosphorylation, impacting T cell responses.

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