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A winged helix forkhead (FOXD2) tunes sensitivity to cAMP in T lymphocytes through regulation of cAMP-dependent

C Christian Johansson1, Maria K Dahle, Sandra Rodrigo Blomqvist

  • 1Department of Medical Biochemistry, Institute of Basic Medical Sciences, University of Oslo, N-0317 Oslo, Norway.

The Journal of Biological Chemistry
|March 7, 2003
PubMed

Insights

Forkhead box D2 (FOXD2) regulates cAMP-dependent protein kinase RIalpha expression in T cells. This regulation impacts T cell proliferation sensitivity to cAMP, influencing immune responses.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • Forkhead/winged helix (FOX) transcription factors are crucial for cell cycle and metabolism regulation.
  • The RIalpha subunit of cAMP-dependent protein kinase plays a role in T cell signaling.

Purpose of the Study:

  • To investigate the role of FOXD2 in regulating RIalpha subunit expression and its functional consequences in T cells.
  • To elucidate the mechanism by which FOXD2 influences cAMP-mediated T cell inhibition.

Main Methods:

  • Analysis of RIalpha mRNA and protein levels in FOXD2 knockout mice.
  • Overexpression studies of FOXD2 in Jurkat T cells.
  • Reporter assays to assess promoter activity.
  • Co-expression experiments with protein kinase Balpha/Akt1.

Main Results:

  • FOXD2 deficiency in mice led to reduced RIalpha mRNA (50%) and protein (35%) levels in spleen.
  • FOXD2 deficiency resulted in decreased sensitivity to cAMP-mediated inhibition of T cell proliferation.
  • FOXD2 overexpression induced RIalpha expression via the RIalpha1b promoter and enhanced promoter sensitivity to cAMP.
  • Protein kinase Balpha/Akt1 synergized with FOXD2 to further induce the RIalpha1b promoter and RIalpha protein levels.

Conclusions:

  • FOXD2 is a physiological regulator of the RIalpha1b promoter in vivo.
  • FOXD2 acts synergistically with protein kinase B to regulate cAMP-dependent protein kinase RIalpha expression.
  • This regulation influences cAMP sensitivity and modulates T cell activation thresholds.

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