Calcium-dependent activation of nuclear factor regulated by interleukin 3/adenovirus E4 promoter-binding protein gene expression by calcineurin/nuclear factor of activated T cells and calcium/calmodulin-dependent protein kinase signaling.
An increase in the intracellular Ca(2+) concentration controls a diverse range of cell functions, including gene expression, apoptosis, adhesion, motility, and proliferation. We have investigated Ca(2+) regulation of gene expression in rat aortic smooth muscle cells. We found that the expression of nuclear factor regulated by interleukin 3 (NFIL3)/adenovirus E4 promoter-binding protein (E4BP4)/basic region/leucine zipper (bZIP) type of a transcription factor that has a very important function in cell survival, was activated by thapsigargin (TG). This activation was inhibited by chelation of extra- or intracellular Ca(2+), suggesting that the induction by TG was dependent on the elevation of [Ca(2+)](i). Specific inhibition of calcineurin or calcium/calmodulin-dependent protein kinase (CaM kinase) by chemical means impaired the TG-induced NFIL3/E4BP4 expression. Expression of dominant negative forms of calcineurin or nuclear factor of activated T cells (NFAT) inhibited the induction of NFIL3/E4BP4 mRNA by TG. These results suggest that intracellular Ca(2+) plays a critical role in regulating gene expression of NFIL3/E4BP4 by calcineurin/NFAT and CaM kinase signaling in vascular smooth muscle cells.
Department of Molecular and Cellular Pharmacology, Mie University School of Medicine, Edobashi, Tsu, Mie 514-8507, Japan.
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Y
Nishimura
T
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Tanaka
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D050976:Basic-Leucine Zipper Transcription Factors; D019703:Calcineurin / Q000502:physiology*; D002118:Calcium / Q000502:physiology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002478:Cells, Cultured; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051790:G-Box Binding Factors; D005786:Gene Expression Regulation / Q000502:physiology*; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors; D051381:Rats; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000201:enzymology / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology; D014158:Transcription, Genetic / Q000502:physiology
D050976:Basic-Leucine Zipper Transcription Factors; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D051790:G-Box Binding Factors; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D014157:Transcription Factors; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019703:Calcineurin; D010749:Phosphoprotein Phosphatases; D002118:Calcium