JNK is involved in signal integration during costimulation of T lymphocytes

Cell. 1994 Jun 3;77(5):727-36. doi: 10.1016/0092-8674(94)90056-6.

Abstract

T lymphocyte activation and interleukin-2 (IL-2) production require at least two signals, generated by phorbol ester (TPA) and Ca2+ ionophore or costimulation of the T cell receptor (TCR) and the CD28 auxiliary receptor. We investigated how these stimuli affect mitogen activated protein (MAP) kinases. Full activation of the MAP kinases that phosphorylate the Jun activation domain, JNK1 and JNK2, required costimulation of T cells with either TPA and Ca2+ ionophore or antibodies to TCR and CD28. Alone, each stimulus resulted in little or no activation. Similar to its effect on IL-2 induction, cyclosporin A (CsA) inhibited the synergistic activation of JNK, and a competitive inhibitor of Jun phosphorylation by JNK inhibited IL-2 promoter activation. By contrast, the MAP kinases ERK1 and ERK2 were fully activated by TPA or TCR stimulation and were not affected by Ca2+, CD28, or CsA. Hence, integration of signals that lead to T cell activation occurs at the level of JNK activation.

Publication types

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

MeSH terms

  • Animals
  • Calcimycin / pharmacology
  • Calcium / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Cell Line
  • Cyclosporine / pharmacology
  • Enzyme Activation
  • Humans
  • JNK Mitogen-Activated Protein Kinases
  • Lymphocyte Activation
  • Mice
  • Mitogen-Activated Protein Kinases*
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins c-jun / biosynthesis
  • Proto-Oncogene Proteins c-jun / metabolism
  • Signal Transduction
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism*
  • Tetradecanoylphorbol Acetate / pharmacology

Substances

  • Proto-Oncogene Proteins c-jun
  • Calcimycin
  • Cyclosporine
  • Protein-Serine-Threonine Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • Tetradecanoylphorbol Acetate
  • Calcium