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

W. Li, C. D. Whaley, J. L. Bonnevier, A. Mondino, M. E. Martin, K. M. Aagaard-Tillery, Daniel L Mueller

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)827-835
Number of pages9
JournalJournal of Immunology
Volume167
Issue number2
DOIs
StatePublished - Jul 15 2001

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