Molecular mechanisms of T lymphocyte activation: convergence of T cell antigen receptor and IL-1 receptor-induced signaling at the level of IL-2 gene transcription
| Autor: | Ursula Dreikhausen, Klaus Resch, Marta Szamel, Annette Appel, Georg Varga, Michael Kracht |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
MAPK/ERK pathway
Transcription Genetic T-Lymphocytes Immunology Receptors Antigen T-Cell Mitogen-activated protein kinase kinase Lymphocyte Activation p38 Mitogen-Activated Protein Kinases MAP2K7 Mice Tumor Cells Cultured Immunology and Allergy Animals ASK1 Mitogen-Activated Protein Kinase Kinases biology MAP kinase kinase kinase Chemistry Cyclin-dependent kinase 5 Cyclin-dependent kinase 2 JNK Mitogen-Activated Protein Kinases Receptors Interleukin-1 General Medicine Molecular biology Cell biology Enzyme Activation Gene Expression Regulation Receptor-CD3 Complex Antigen T-Cell biology.protein Interleukin-2 Cyclin-dependent kinase 9 Mitogen-Activated Protein Kinases Signal Transduction Transcription Factors |
| Zdroj: | International immunology. 11(11) |
| ISSN: | 0953-8178 |
| Popis: | Co-stimulation of murine EL-4 thymoma cells-carrying high numbers of TCR and type I IL-1 receptors (IL-1R)-with anti-CD3 antibodies and IL-1 resulted in synergistic enhancement of IL-2 synthesis. While the extracellular signal-regulated kinase (ERK) cascade was activated by both receptors, IL-1 preferentially stimulated Jun-N-terminal kinases (JNK) and p38 mitogen-activated kinase or microtubule-associated protein kinase (MAPK). Interruption of TCR- or IL-1R-stimulated ERK cascade by PD-98059, a specific inhibitor of MAP/ERK kinase (MEK), resulted in partial suppression of nuclear factor of activated T cells activation and in complete inhibition of IL-1-stimulated NFkappaB activation. Suppression of activation of both MEK and p38 MAPK resulted in significant inhibition of IL-2 gene expression. The results show that maximal activation of the IL-2 gene requires activation of at least two different protein kinase cascades, i.e. of the ERK and p38 pathways but presumably also that of JNK which converge at the level of the IL-2 promoter resulting in enhancement of its transcriptional activity. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|