MEF2C regulates c-Jun but not TNF-alpha gene expression in stimulated mast cells
| Autor: | Anthony Joetham, Gary L. Johnson, Erwin W. Gelfand, Weiyong Sun, Ruihua Fan, Timothy P. Garrington, Xudong Wei, Saiphone Webb, Joseph J. Lucas, Guiming Li, Joanne Hahn, Azzeddine Dakhama |
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| Rok vydání: | 2003 |
| Předmět: |
MAPK/ERK pathway
Immunology MAP Kinase Kinase 7 MAP Kinase Kinase 5 MAP Kinase Kinase Kinase 2 Immunoglobulin E Mice Genes jun Immunology and Allergy Animals Mast Cells Mast cell cytokine production Phosphorylation Protein kinase A Mitogen-Activated Protein Kinase 7 Mitogen-Activated Protein Kinase Kinases biology Kinase MEF2 Transcription Factors Tumor Necrosis Factor-alpha c-jun MAP Kinase Kinase Kinases Cell biology Interleukin 33 Gene Expression Regulation Myogenic Regulatory Factors biology.protein Signal transduction Mitogen-Activated Protein Kinases |
| Zdroj: | European journal of immunology. 33(10) |
| ISSN: | 0014-2980 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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