Other
12 Authors
- Wei X,
- Li G,
- Fan R,
- Joetham A,
- Sun W,
- Lucas J,
- Johnson GL,
- Garrington T,
- Webb S,
- Gelfand EW,
- Dakhama A,
- Hahn J
| First Author | Wei X | Year | 2003 |
| Journal | Eur J Immunol | Volume | 33 |
| Issue | 10 | Pages | 2903-9 |
| PubMed ID | 14515274 | Mgi Jnum | J:175200 |
| Mgi Id | MGI:5284808 | Doi | 10.1002/eji.200324127 |
| Citation | Wei X, et al. (2003) MEF2C regulates c-Jun but not TNF-alpha gene expression in stimulated mast cells. Eur J Immunol 33(10):2903-9 |
| abstractText | 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 (FcepsilonRI). 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-alpha. 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 FcepsilonRI 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 FcepsilonRI, a pathway distinct from that involving MEKK2-MEK5-ERK5 in the regulation of mast cell cytokine production. |
