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Down-regulation of lck mRNA by T cell activation involves transcriptional and post-transcriptional mechanisms

F Paillard1, C Vaquero

  • 1U 152 INSERM, ICGM, Hopital Cochin, Paris, France.

Nucleic Acids Research
|September 11, 1991
PubMed

Insights

The p56lck tyrosine kinase regulates T cell activation. Its mRNA levels decrease after activation due to reduced transcription and stability, a process influenced by protein synthesis and specific regulatory factors.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Signaling

Background:

  • p56lck tyrosine kinase is crucial for T lymphocyte activation via the TcR/CD3 complex.
  • Following T cell activation, lck mRNA expression is transiently downregulated.
  • This downregulation results from decreased lck mRNA transcription and stability.

Purpose of the Study:

  • To investigate the roles of transcriptional and post-transcriptional factors in regulating lck mRNA levels.
  • To elucidate the mechanisms behind lck mRNA downregulation after T cell activation.

Main Methods:

  • Analysis of lck mRNA steady-state using cycloheximide, a protein synthesis inhibitor.
  • Assessment of lck mRNA transcription and stability under various conditions.
  • Evaluation of Cyclosporin A's effect on lck mRNA regulation.

Main Results:

  • Cycloheximide increased lck mRNA stability and overall levels, despite decreasing transcription, suggesting negative post-transcriptional regulation at the constitutive level.
  • Cycloheximide inhibited lck mRNA downregulation post-activation by stabilizing the mRNA, indicating activation enhances destabilizing factors.
  • Cyclosporin A inhibited lck mRNA downregulation by increasing transcription, without affecting stability, and shared regulatory pathways with lymphokine induction.

Conclusions:

  • Constitutive lck mRNA levels are maintained by transcriptional activators and post-transcriptional destabilizers.
  • T cell activation likely involves increased synthesis or activity of mRNA destabilizing factors.
  • Common regulatory pathways may govern the inverse transcriptional regulation of lck and lymphokine genes.

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