Calmodulin dependence of NFkappaB activation.
The NFkappaB family of transcription factors is regulated by inhibitory IkappaB proteins. A diversity of stimuli leads to the phosphorylation and subsequent degradation of IkappaB, releasing NFkappaB to act on its target genes. Calmodulin (CaM) is a key regulator of numerous cellular processes and is the predominant intracellular receptor for Ca2+ signals. Here we report that several CaM antagonists inhibit the activation of NFkappaB, and that this is due to the prevention of inducible IkappaB phosphorylation. Our results suggest that CaM is involved in the phosphorylation of IkappaB, a finding that may help in elucidating the mechanism of this critical step of NFkappaB activation.
Hughes
K
K
Department of Cell and Molecular Biology, Umeå University, Sweden.
Antonsson
A
A
Grundstrøm
T
T
D000818:Animals; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016572:Cyclosporine / Q000494:pharmacology; D017930:Genes, Reporter; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D019169:Jurkat Cells; D007700:Kinetics; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis; D013449:Sulfonamides / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D051841:Transcription Factor RelB; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection
D002147:Calmodulin; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; C497593:RELB protein, human; D011994:Recombinant Proteins; C497594:Relb protein, mouse; D013449:Sulfonamides; D014157:Transcription Factors; D051841:Transcription Factor RelB; D015759:Ionomycin; C017967:W 7; D016572:Cyclosporine; D008156:Luciferases; D013755:Tetradecanoylphorbol Acetate