Stabilization of interleukin-2 mRNA by the c-Jun NH2-terminal kinase pathway

Science. 1998 Jun 19;280(5371):1945-9. doi: 10.1126/science.280.5371.1945.

Abstract

Signaling pathways that stabilize interleukin-2 (IL-2) messenger RNA (mRNA) in activated T cells were examined. IL-2 mRNA contains at least two cis elements that mediated its stabilization in response to different signals, including activation of c-Jun amino-terminal kinase (JNK). This response was mediated through a cis element encompassing the 5' untranslated region (UTR) and the beginning of the coding region. IL-2 transcripts lacking this 5' element no longer responded to JNK activation but were still responsive to other signals generated during T cell activation, which were probably sensed through the 3' UTR. Thus, multiple elements within IL-2 mRNA modulate its stability in a combinatorial manner, and the JNK pathway controls turnover as well as synthesis of IL-2 mRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD28 Antigens / immunology
  • CD3 Complex / immunology
  • Calcimycin / pharmacology
  • Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Cyclosporine / pharmacology
  • Enzyme Activation
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Regulation*
  • Humans
  • Imidazoles / pharmacology
  • Interleukin-2 / genetics*
  • JNK Mitogen-Activated Protein Kinases
  • Jurkat Cells
  • Lymphocyte Activation
  • MAP Kinase Kinase 1
  • MAP Kinase Kinase 7
  • Mitogen-Activated Protein Kinase Kinases*
  • Mitogen-Activated Protein Kinases*
  • Protein Kinases / metabolism
  • Protein Serine-Threonine Kinases / metabolism
  • Protein-Tyrosine Kinases / metabolism
  • Pyridines / pharmacology
  • RNA, Messenger / chemistry
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • Signal Transduction
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • Tetradecanoylphorbol Acetate / pharmacology
  • Transgenes
  • p38 Mitogen-Activated Protein Kinases

Substances

  • CD28 Antigens
  • CD3 Complex
  • Enzyme Inhibitors
  • Imidazoles
  • Interleukin-2
  • Pyridines
  • RNA, Messenger
  • Calcimycin
  • Cyclosporine
  • Protein Kinases
  • Protein-Tyrosine Kinases
  • Protein Serine-Threonine Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 1
  • MAP Kinase Kinase 7
  • MAP2K1 protein, human
  • MAP2K7 protein, human
  • Mitogen-Activated Protein Kinase Kinases
  • Tetradecanoylphorbol Acetate
  • 4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole