MEF2C regulates c-Jun but not TNF-α gene expression in stimulated mast cells

Xudong Wei, Weiyong Sun, Ruihua Fan, Joanne Hahn, Anthony Joetham, Guiming Li, Saiphone Webb, Timothy Garrington, Azzeddine Dakhama, Joseph Lucas, Gary L. Johnson, Erwin W. Gelfand

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Mitogen-activated protein kinase (MAPK) cascades play essential roles in the transduction of extracellular signals to cytoplasmic and nuclear effectors. The MAPK kinase kinase MEKK2 is essential for activation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase 5 (ERK5). These pathways are important for expression of specific cytokine genes in mast cells following cross-linking of the high-affinity IgE receptor (FcERI). A consequence of ERK5 activation is activation of the transcriptional factor myocyte enhancing factor-2C (MEF2C), leading to increased c-Jun expression. We have investigated the role of MEF2C activation in mast cells and demonstrated that it requires sequential activation of the signaling cascade of MEKK2-MEK5-ERK5. Following phosphorylation of MEF2C, activated MEF2C regulates transcription of c-Jun but not TNF-α. Inhibition of ERK5, MEK5 activation or activation of MEKK2-deficient mast cells was associated with inhibition of MEF2C phosphorylation and a decrease in c-Jun expression. Thus, these data define an activation module, MEKK2-MEK5-ERK5-MEF2C in the transcriptional activation of c-Jun in mast cells following FcERI cross-linking. These results demonstrate the novel and important, MEKK2-dependent role of MEF2C in induction of c-Jun expression in mast cells activated through FcERI, a pathway distinct from that involving MEKK2-MEK5-ERK5 in the regulation of mast cell cytokine production.

Original languageEnglish (US)
Pages (from-to)2903-2909
Number of pages7
JournalEuropean Journal of Immunology
Volume33
Issue number10
DOIs
StatePublished - Oct 1 2003

Keywords

  • Mast cells
  • Protein kinases
  • Signal transduction

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Wei, X., Sun, W., Fan, R., Hahn, J., Joetham, A., Li, G., Webb, S., Garrington, T., Dakhama, A., Lucas, J., Johnson, G. L., & Gelfand, E. W. (2003). MEF2C regulates c-Jun but not TNF-α gene expression in stimulated mast cells. European Journal of Immunology, 33(10), 2903-2909. https://doi.org/10.1002/eji.200324127