CD28 signaling augments Elk-1-dependent transcription at the c-fos gene during antigen stimulation.
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.
Li
W
W
Department of Medicine, Rheumatic and Autoimmune Diseases Section, and Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
Whaley
C D
CD
Bonnevier
J L
JL
Mondino
A
A
Martin
M E
ME
Aagaard-Tillery
K M
KM
Mueller
D L
DL
D000276:Adjuvants, Immunologic / Q000502:physiology*; D000818:Animals; D017951:Antigen Presentation; D000941:Antigens / Q000276:immunology*; D018122:B7-1 Antigen / Q000378:metabolism / Q000502:physiology; D018106:CD28 Antigens / Q000378:metabolism / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000502:physiology; D004742:Enhancer Elements, Genetic / Q000276:immunology; D004789:Enzyme Activation / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D016762:Genes, fos / Q000276:immunology*; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics; D048031:JNK Mitogen-Activated Protein Kinases; D019169:Jurkat Cells; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology*; D048369:MAP Kinase Kinase 1; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020929:Mitogen-Activated Protein Kinase Kinases; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology*; D018417:Th1 Cells / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology; D014158:Transcription, Genetic / Q000276:immunology*; D015533:Transcriptional Activation / Q000276:immunology; D050807:ets-Domain Protein Elk-1
D000276:Adjuvants, Immunologic; D000941:Antigens; D018122:B7-1 Antigen; D018106:CD28 Antigens; D004268:DNA-Binding Proteins; C494112:ELK1 protein, human; C494113:Elk1 protein, mouse; D007376:Interleukin-2; D008024:Ligands; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1; D017346:Protein Serine-Threonine Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048369:MAP Kinase Kinase 1; C482125:MAP2K1 protein, human; C482127:Map2k1 protein, mouse; D020929:Mitogen-Activated Protein Kinase Kinases