Role of MEKK2-MEK5 in the regulation of TNF-α gene expression and MEKK2-MKK7 in the activation of c-Jun N-terminal kinase in mast cells
| Autor: | Soula Ganiatsas, Timothy P. Garrington, Philip J. Papst, Tamotsu Ishizuka, Gary L. Johnson, Kosuke Chayama, Saiphone Webb, Erwin W. Gelfand, Joanne C. Pratt, Leonard I. Zon, Weiyong Sun |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2001 |
| Předmět: |
MAPK7
MAP Kinase Kinase 7 Mitogen-activated protein kinase kinase MAP Kinase Kinase 5 MAP Kinase Kinase Kinase 2 MAP2K7 Cell Line ASK1 Mast Cells Promoter Regions Genetic MAPK14 Mitogen-Activated Protein Kinase Kinases Multidisciplinary biology MAP kinase kinase kinase Cyclin-dependent kinase 4 Chemistry Tumor Necrosis Factor-alpha JNK Mitogen-Activated Protein Kinases Biological Sciences MAP Kinase Kinase Kinases Cell biology Enzyme Activation Gene Expression Regulation biology.protein Cancer research Cyclin-dependent kinase 9 Mitogen-Activated Protein Kinases |
| Popis: | Cross-linking of the high-affinity IgE receptor (FcepsilonRI) on mast cells with IgE and multivalent antigen triggers mitogen-activated protein (MAP) kinase activation and cytokine gene expression. We report here that MAP kinase kinase 4 (MKK4) gene disruption does not affect either MAP kinase activation or cytokine gene expression in response to cross-linking of FcepsilonRI in embryonic stem cell-derived mast cells. MKK7 is activated in response to cross-linking of FcepsilonRI, and this activation is inhibited by MAP/ERK kinase (MEK) kinase 2 (MEKK2) gene disruption. In addition, expression of kinase-inactive MKK7 in the murine mast cell line MC/9 inhibits c-Jun NH(2)-terminal kinase (JNK) activation in response to cross-linking of FcepsilonRI, whereas expression of kinase-inactive MKK4 does not affect JNK activation by this stimulus. However, FcepsilonRI-induced activation of the tumor necrosis factor-alpha (TNF-alpha) gene promoter is not affected by expression of kinase-inactive MKK7. We describe an alternative pathway by which MEKK2 activates MEK5 and big MAP kinase1/extracellular signal-regulated kinase 5 in addition to MKK7 and JNK, and interruption of this pathway inhibits TNF-alpha promoter activation. These findings suggest that JNK activation by antigen cross-linking is dependent on the MEKK2-MKK7 pathway, and cytokine production in mast cells is regulated in part by the signaling complex MEKK2-MEK5-ERK5. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|