Protein kinase C-theta participates in the activation of cyclic AMP-responsive element-binding protein and its subsequent binding to the -180 site of the IL-2 promoter in normal human T lymphocytes

The Journal of Immunology : Official Journal of the American Association of Immunologists
E E SolomouG C Tsokos

Abstract

IL-2 gene expression is regulated by the cooperative binding of discrete transcription factors to the IL-2 promoter/enhancer and is predominantly controlled at the transcriptional level. In this study, we show that in normal T cells, the -180 site (-164/-189) of the IL-2 promoter/enhancer is a p-cAMP-responsive element-binding protein (p-CREB) binding site. Following activation of the T cells through various membrane-initiated and membrane-independent pathways, protein kinase C (PKC)-theta phosphorylates CREB, which subsequently binds to the -180 site and associates with the transcriptional coactivator p300. Rottlerin, a specific PKC-theta inhibitor, diminished p-CREB protein levels when normal T cells were treated with it. Rottlerin also prevented the formation of p-CREB/p300 complexes and the DNA-CREB protein binding. Cotransfection of fresh normal T cells with luciferase reporter construct driven by two tandem -180 sites and a PKC-theta construct caused a significant increase in the transcription of the reporter gene, indicating that this site is functional and regulated by PKC-theta. Cotransfection of T cells with a luciferase construct driven by the -575/+57 region of the IL-2 promoter/enhancer and a PKC-theta construct ca...Continue Reading

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Citations

Feb 28, 2002·Annual Review of Immunology·Noah Isakov, Amnon Altman
Mar 11, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Klaus TenbrockGeorge C Tsokos
Nov 8, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yuang-Taung JuangG C Tsokos
Jan 18, 2007·The Journal of Biological Chemistry·Jinghua WangSabita Roy
Nov 10, 2012·ChemMedChem·Loek T M van WandelenRob M J Liskamp
Nov 19, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Andy Y WenLloyd S Miller
Mar 9, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yuang-Taung JuangGeorge C Tsokos
Oct 9, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Klaus TenbrockGeorge C Tsokos
Mar 22, 2003·The Journal of Pharmacology and Experimental Therapeutics·Peter H SchaferDavid I Stirling
Aug 31, 2007·Autoimmunity·Paul E Zarek, Jonathan D Powell
May 18, 2011·World Journal of Gastrointestinal Pharmacology and Therapeutics·Javier EscobarJuan Sastre
Jun 19, 2004·International Reviews of Immunology·Klaus Tenbrock, George C Tsokos
Aug 3, 2007·European Journal of Immunology·Madlen KaiserAndrew Macdonald
Jul 21, 2009·Chembiochem : a European Journal of Chemical Biology·Alex J PootRob M J Liskamp
Jun 15, 2011·The Journal of Biological Chemistry·María Rosa López-HuertasMayte Coiras
Oct 21, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Klaus TenbrockGeorge C Tsokos
Jun 28, 2019·Frontiers in Immunology·Selena ViganoGeorge Coukos
Jun 23, 2007·Journal of Photochemistry and Photobiology. B, Biology·Roberta RigolioCorrado Maria Cilio

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