Overexpression of mitogen-activated protein kinase kinase kinase reversed cAMP inhibition of NF-kappaB in T cells

Eur J Immunol. 1997 Jan;27(1):222-6. doi: 10.1002/eji.1830270133.

Abstract

cAMP inhibits T cell activation by acting as an antagonist for selective kinases and transcriptional factors. We have recently demonstrated that cAMP inhibited c-Jun N-terminal kinase (JNK) but left the mitogen-activated protein (MAP) kinase cascade almost unaffected in T lymphocytes. In accordance with recent reports, we also observed a selective suppression of nuclear factor NF-kappaB activation by cAMP. The possible link between the JNK cascade and NF-kappaB activation was demonstrated by the fact that the active form of MAP kinase kinase kinase (deltaMEKK), a constitutive activator of JNK, induced NF-kappaB but not AP-1, Oct, and NF-AT in T cells. In contrast, the induction of MAP kinase kinase (MEK)-MAP kinase did not stimulate NF-kappaB activity. The specific activation of NF-kappaB by a single MEKK-JNK cascade was thus unusual, given that the activation of other transcriptional elements in T cells requires at least two signal pathways. This was further confirmed by the fact that cAMP inhibition of NF-kappaB activation was reversed by overexpression of deltaMEKK.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cyclic AMP / antagonists & inhibitors*
  • DNA-Binding Proteins / antagonists & inhibitors
  • Fetal Proteins / metabolism
  • Gene Expression Regulation / drug effects
  • Host Cell Factor C1
  • JNK Mitogen-Activated Protein Kinases*
  • MAP Kinase Kinase 4
  • MAP Kinase Kinase Kinases
  • Mice
  • Mitogen-Activated Protein Kinase Kinases*
  • NF-kappa B / antagonists & inhibitors*
  • NFATC Transcription Factors
  • Nuclear Proteins*
  • Octamer Transcription Factor-1
  • Protein Kinases / metabolism
  • Protein Serine-Threonine Kinases / physiology*
  • Proto-Oncogene Proteins / physiology
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Receptor, EphA4
  • Signal Transduction
  • T-Lymphocytes / physiology*
  • Transcription Factor AP-1 / antagonists & inhibitors
  • Transcription Factor RelB
  • Transcription Factors / antagonists & inhibitors

Substances

  • DNA-Binding Proteins
  • Fetal Proteins
  • Hcfc1 protein, mouse
  • Host Cell Factor C1
  • NF-kappa B
  • NFATC Transcription Factors
  • Nuclear Proteins
  • Octamer Transcription Factor-1
  • Pou2f1 protein, mouse
  • Proto-Oncogene Proteins
  • Relb protein, mouse
  • Transcription Factor AP-1
  • Transcription Factors
  • Transcription Factor RelB
  • Cyclic AMP
  • Protein Kinases
  • Receptor Protein-Tyrosine Kinases
  • Receptor, EphA4
  • Protein Serine-Threonine Kinases
  • JNK Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase Kinases
  • MAP Kinase Kinase 4
  • Mitogen-Activated Protein Kinase Kinases