The Jun Kinase Cascade Is Responsible for Activating the CD28 Response Element of the IL-2 Promoter: Proof of Cross-Talk with the IκB Kinase Cascade
| Autor: | Stephan J. Kempiak, Timothy S. Hiura, Andre E. Nel |
|---|---|
| Rok vydání: | 1999 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 162:3176-3187 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.162.6.3176 |
| Popis: | Costimulation of TCR/CD3 and CD28 receptors leads to activation of the Jun kinase (JNK) cascade, which plays a key role in T cell activation, including activation of the IL-2 promoter. We demonstrate that the JNK cascade plays a central role in the activation of the CD28 response element (CD28RE) in the IL-2 promoter. This response element is linked to an activating protein-1 (AP-1) site, which functions synergistically with the CD28RE. The role of the JNK cascade in the activation of this composite element is twofold: 1) activation of the AP-1 site through transcriptional activation of c-Jun, and 2) activation of the CD28RE through selective cross-talk with IκB kinase-β (IKKβ). Dominant-negative versions of JNK kinase, c-Jun, and IKKβ interfered in CD3- plus CD28-induced CD28RE/AP-1 luciferase activity in Jurkat cells. In contrast, the dominant-active JNK kinase kinase, MEKK1, induced CD28RE/AP-1 luciferase activity, in parallel with induction of c-Jun and c-Rel binding to this combined promoter site. Dominant-active MEKK1 also induced transfected IKKβ, but not IKKα, activity. In contrast to the JNK cascade, the extracellular signal-regulated kinase (ERK) cascade did not exert an affect on the CD28RE/AP-1 site, but did contribute to activation of the distal NF-AT/AP-1 site. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|