CD28 Signaling Augments Elk-1-Dependent Transcription at the c-fos Gene During Antigen Stimulation

• Published in: The Journal of immunology (1950) Vol. 167; no. 2; pp. 827 - 835
• Main Authors: Li, Wei, Whaley, Carmella D, Bonnevier, Jody L, Mondino, Anna, Martin, Molly E, Aagaard-Tillery, Kjersti M, Mueller, Daniel L
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.07.2001
• Subjects: Adjuvants, Immunologic - physiology; Animals; Antigen Presentation; Antigens - immunology; B7-1 Antigen - metabolism; B7-1 Antigen - physiology; c-Fos protein; CD28 antigen; CD28 Antigens - metabolism; CD28 Antigens - physiology; DNA-Binding Proteins - physiology; Elk-1 protein; Enhancer Elements, Genetic - immunology; Enzyme Activation - immunology; ets-Domain Protein Elk-1; Gene Expression Regulation - immunology; Genes, fos - immunology; Humans; Interleukin-2 - genetics; JNK Mitogen-Activated Protein Kinases; JNK protein; 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
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.167.2.827

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.