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Related Experiment Videos

CD28-costimulation activates cyclic AMP-responsive element-binding protein in T lymphocytes

Y P Hsueh1, H E Liang, S Y Ng

  • 1Graduate Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan.

Journal of Immunology (Baltimore, Md. : 1950)
|January 1, 1997
PubMed
Summary

Cyclic AMP-responsive element binding protein (CREB) requires both Ser133 phosphorylation and CD28 costimulation for full T cell activation and IL-2 gene expression. A mitogen-activated protein kinase kinase pathway is involved in this dual signaling process.

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Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Signaling

Background:

  • Cyclic AMP-responsive element binding protein (CREB) regulates gene expression following cAMP stimulation.
  • CREB transcriptional activity is contingent upon Ser133 phosphorylation and cofactor recruitment.
  • T cell activation involves CREB phosphorylation essential for Interleukin-2 (IL-2) gene expression.

Purpose of the Study:

  • To investigate the signaling pathways governing CREB-mediated gene expression during T cell activation.
  • To determine if CREB phosphorylation at Ser133 is sufficient for transcriptional activity.
  • To elucidate the role of CD28 costimulation in enhancing CREB activity.

Main Methods:

  • Stimulation of T cells with anti-CD3 and/or CD28 antibodies or O-tetradecanoylphorbol 13-acetate.

Related Experiment Videos

  • Assessment of CREB transcriptional activity using a CRE-dependent reporter gene and GAL4-CREB fusion protein.
  • Inhibition of specific kinase pathways using selective inhibitors.

    • Main Results:

    • While Ser133 phosphorylation of CREB occurred during T cell activation, it was insufficient for full transcriptional activity.
    • CD28 costimulation, in conjunction with anti-CD3 or O-tetradecanoylphorbol 13-acetate, significantly enhanced CREB-mediated gene expression.
    • The dual signaling pathway involved mitogen-activated protein kinase kinase, but not protein kinase C, protein kinase A, or p70 S6 kinase.

    Conclusions:

    • Optimal CREB induction and T cell activation require two distinct signals, including CD28 costimulation.
    • CD28 provides a critical second signal necessary for robust CREB-mediated gene expression, particularly IL-2 production.
    • Mitogen-activated protein kinase kinase is a key component of the CD28-dependent pathway activating CREB.