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Regulation of the human atrial myosin light chain 1 promoter by Ca 2+ ‐calmodulin‐dependent signaling pathways
Author(s) -
Woischwill Christiane,
Karczewski Peter,
Bartsch Holger,
Luther Hans-Peter,
Kott Monika,
Haase Hannelore,
Morano Ingo
Publication year - 2005
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.04-2201com
Subject(s) - nfat , camk , calcineurin , calmodulin , myosin light chain kinase , protein kinase c , signal transduction , microbiology and biotechnology , biology , hek 293 cells , kinase , phosphorylation , protein kinase a , chemistry , transcription factor , gene , biochemistry , medicine , enzyme , autophosphorylation , transplantation
We investigated expression regulation of the human atrial myosin light chain 1 (hALC‐1) gene using a cardiomyocyte H9c2 cell line stably transfected with a construct consisting of the human ALC‐1 promoter cloned in front of the luciferase gene (H9c2T1). H9c2T1 cells were stimulated with vasopressin, which is known to induce cardiomyocyte hypertrophy and to activate a panel of signaling pathways. Those pathways involved in hALC‐1 promoter activity regulation were dissected by using pharmacological inhibitor substances. Stimulation with vasopressin was associated with nuclear NFAT translocation and significantly increased human ALC‐1 promoter activity. Inhibition of calcineurin by cyclosporin A blocked the effects of vasopressin on ALC‐1 promoter activity to ~50%. This suggests that the Ca 2+ ‐calmodulin‐calcineurin‐NFAT pathway is involved in human ALC‐1 promoter activation. However, inhibition of multifunctional Ca 2+ ‐calmodulin‐dependent protein kinases (CaMK) by KN‐93 decreased human ALC‐1 promoter activity to almost basal levels. CaMK regulation of ALC‐1 promoter activity effect could well be mediated by CaMKIV, which accumulated in the nucleus upon vasopressin stimulation. Inhibition of protein kinase C (PKC) isoforms by bisindolylmaleimide had no significant influence on human ALC‐1 promoter activity. Thus, our results demonstrate a dominant role of Ca 2+ ‐calmodulin‐dependent signaling pathways in the regulation of human ALC‐1 expression.ȁWoischwill, C., Karczewski, P., Bartsch, H., Luther, H.‐P., Kott, M., Haase, H., Morano, I. Regulation of the human atrial myosin light chain 1 promoter by Ca2+‐calmodulin‐dependent signaling pathways. FASEB J . 19, 503–511 (2005)