GADD45gamma mediates the activation of the p38 and JNK MAP kinase pathways and cytokine production in effector TH1 cells

Immunity. 2001 May;14(5):583-90. doi: 10.1016/s1074-7613(01)00141-8.


The p38 and JNK stress-activated MAPK signal transduction pathways are activated by T cell receptor (TCR) signaling and are required for IFN-gamma production by TH1 effector cells. Here, we show that the expression of GADD45gamma is induced during T cell activation and that the level of expression is higher in TH1 cells than in TH2 cells. TH1 cells from GADD45gamma(-/-) mice are severely compromised in their abilities to activate p38 and JNK in response to TCR signaling, produce much less IFN-gamma upon restimulation, and are deficient in activation-induced cell death (AICD). Additionally, GADD45gamma deficiencies caused reduced contact hypersensitivity in mice. Thus, GADD45gamma mediates activation of the p38 and JNK pathways and effector function of TH1 cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, CD / biosynthesis
  • Apoptosis / immunology
  • Biomarkers
  • CD4-Positive T-Lymphocytes / immunology
  • Cells, Cultured
  • Cytokines / biosynthesis
  • Enzyme Activation
  • Humans
  • Interferon-gamma / biosynthesis*
  • Interleukin-12 / immunology
  • Interleukin-4 / immunology
  • Intracellular Signaling Peptides and Proteins
  • JNK Mitogen-Activated Protein Kinases
  • Mice
  • Mice, Knockout
  • Mitogen-Activated Protein Kinases / immunology*
  • Mitogen-Activated Protein Kinases / metabolism
  • Proteins / genetics
  • Proteins / immunology*
  • Signal Transduction / immunology*
  • Th1 Cells / immunology*
  • Th2 Cells / immunology
  • p38 Mitogen-Activated Protein Kinases


  • Antigens, CD
  • Biomarkers
  • Cytokines
  • GADD45 protein
  • Intracellular Signaling Peptides and Proteins
  • Proteins
  • Interleukin-12
  • Interleukin-4
  • Interferon-gamma
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases