CD28 signaling augments Elk-1-dependent transcription at the c-fos gene during antigen stimulation

J Immunol. 2001 Jul 15;167(2):827-35. doi: 10.4049/jimmunol.167.2.827.

Abstract

Untransformed CD4(+) Th1 cells stimulated with Ag and APC demonstrated a dependence on B7- and CD28-mediated costimulatory signals for the expression and function of AP-1 proteins. The induction of transactivation by the c-fos gene regulator Elk-1 mirrored this requirement for TCR and CD28 signal integration. c-Jun N-terminal kinase (JNK) (but not extracellular signal-regulated kinase or p38) protein kinase activity was similarly inhibited by neutralizing anti-B7 mAbs. Blockade of JNK protein kinase activity with SB 202190 prevented both Elk-1 transactivation and c-Fos induction. These results identify a unique role for B7 costimulatory molecules and CD28 in the activation of JNK during Ag stimulation in Th1 cells, and suggest that JNK regulates Elk-1 transactivation at the c-fos gene to promote the formation of AP-1 complexes important to IL-2 gene expression.

Publication types

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

MeSH terms

  • Adjuvants, Immunologic / physiology*
  • Animals
  • Antigen Presentation
  • Antigens / immunology*
  • B7-1 Antigen / metabolism
  • B7-1 Antigen / physiology
  • CD28 Antigens / metabolism
  • CD28 Antigens / physiology*
  • DNA-Binding Proteins / physiology
  • Enhancer Elements, Genetic / immunology
  • Enzyme Activation / immunology
  • Gene Expression Regulation / immunology
  • Genes, fos / immunology*
  • Humans
  • Interleukin-2 / genetics
  • JNK Mitogen-Activated Protein Kinases
  • Jurkat Cells
  • Ligands
  • Lymphocyte Activation / immunology*
  • MAP Kinase Kinase 1
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mitogen-Activated Protein Kinase Kinases
  • Mitogen-Activated Protein Kinases / metabolism
  • NFATC Transcription Factors
  • Nuclear Proteins*
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins / physiology*
  • Signal Transduction / immunology*
  • Th1 Cells / enzymology
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Transcription Factor AP-1 / biosynthesis
  • Transcription Factor AP-1 / metabolism
  • Transcription Factor AP-1 / physiology
  • Transcription Factors / physiology
  • Transcription, Genetic / immunology*
  • Transcriptional Activation / immunology
  • ets-Domain Protein Elk-1

Substances

  • Adjuvants, Immunologic
  • Antigens
  • B7-1 Antigen
  • CD28 Antigens
  • DNA-Binding Proteins
  • ELK1 protein, human
  • Elk1 protein, mouse
  • Interleukin-2
  • Ligands
  • NFATC Transcription Factors
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • Transcription Factor AP-1
  • Transcription Factors
  • ets-Domain Protein Elk-1
  • Protein-Serine-Threonine Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 1
  • MAP2K1 protein, human
  • Map2k1 protein, mouse
  • Mitogen-Activated Protein Kinase Kinases