TRESK channel as a potential target to treat T-cell mediated immune dysfunction.
In this review, we propose that TRESK background K(+) channel could serve as a potential therapeutic target for T-cell mediated immune dysfunction. TRESK has many immune function-related properties. TRESK is abundantly expressed in the thymus, the spleen, and human leukemic T-lymphocytes. TRESK is highly activated by Ca(2+), calcineurin, acetylcholine, and histamine which induce hypertrophy, whereas TRESK is inhibited by immunosuppressants, such as cyclosporin A and FK506. Cyclosporine A and FK506 target the binding site of nuclear factor of activated T-cells (NFAT) to inhibit calcineurin. Interestingly, TRESK possesses an NFAT-like docking site that is present at its intracellular loop. Calcineurin has been found to interact with TRESK via specific NFAT-like docking site. When the T-cell is activated, calcineurin can bind to the NFAT-docking site of TRESK. The activation of both TRESK and NFAT via Ca(2+)-calcineurin-NFAT/TRESK pathway could modulate the transcription of new genes in addition to regulating several aspects of T-cell function.
Medical Research Center for Neural Dysfunction, Department of Physiology, Institute of Health Sciences, Gyeongsang National University, School of Medicine, Jinju 660-751, Republic of Korea.
Jaehee
J
Han
Dawon
D
Kang
D019703:Calcineurin / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology; D006801:Humans; D007154:Immune System Diseases / Q000188:drug therapy*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D050778:NFATC Transcription Factors / Q000378:metabolism; D015221:Potassium Channels / Q000819:agonists / Q000187:drug effects* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D016559:Tacrolimus / Q000494:pharmacology
D007166:Immunosuppressive Agents; C476574:KCNK18 protein, human; D050778:NFATC Transcription Factors; D015221:Potassium Channels; D016572:Cyclosporine; D019703:Calcineurin; D002118:Calcium; D016559:Tacrolimus