The Jun kinase cascade is responsible for activating the CD28 response element of the IL-2 promoter: proof of cross-talk with the I kappa B kinase cascade.
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 I kappa B kinase-beta (IKK beta). Dominant-negative versions of JNK kinase, c-Jun, and IKK beta 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 IKK beta, but not IKK alpha, 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.
Kempiak
S J
SJ
Department of Medicine, University of California, School of Medicine, Los Angeles 90095, USA.
Hiura
T S
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Nel
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D018106:CD28 Antigens / Q000235:genetics* / Q000378:metabolism*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism* / Q000502:physiology; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D051550:I-kappa B Kinase; D007376:Interleukin-2 / Q000235:genetics* / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases; D019169:Jurkat Cells; D048728:MAP Kinase Kinase Kinase 1; D020928:Mitogen-Activated Protein Kinases; D011401:Promoter Regions, Genetic / Q000276:immunology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D020218:Response Elements / Q000276:immunology*; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism
D018106:CD28 Antigens; D007376:Interleukin-2; D018808:Transcription Factor AP-1; D017346:Protein Serine-Threonine Kinases; C496559:CHUK protein, human; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C496565:IKBKE protein, human; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048728:MAP Kinase Kinase Kinase 1; C482576:MAP3K1 protein, human