Evidence for a functional interaction between calmodulin and the glucocorticoid receptor.
In the signaling cascade of membrane-bound receptors, calmodulin (CaM) plays an important role. However, little is known about the role of CaM in the activation of intracellular steroid receptors, which are known to act as ligand-regulated transcription factors. We report here that CaM can interact in a calcium-dependent manner with the untransformed glucocorticoid receptor (GR) complex containing hsp90. In addition, we demonstrate that four unrelated CaM antagonists (trifluoperazine, compound 48/80, W7, and phenoxybenzamine) can inhibit GR-mediated gene expression in mouse L929 cells stably-transfected with the MMTV-CAT reporter gene. These results provide evidence that CaM may play an important role in the signal transduction pathways of steroid hormone receptors.
Ning
Y M
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Department of Pharmacology, Medical College of Ohio, Toledo 43699.
Sánchez
E R
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D000818:Animals; D015153:Blotting, Western; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015500:Chloramphenicol O-Acetyltransferase / Q000378:metabolism; D002846:Chromatography, Affinity; D003600:Cytosol / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D018841:HSP90 Heat-Shock Proteins / Q000302:isolation & purification / Q000378:metabolism; D007700:Kinetics; D007739:L Cells; D051379:Mice; D010643:Phenoxybenzamine / Q000494:pharmacology; D011965:Receptors, Glucocorticoid / Q000302:isolation & purification / Q000378:metabolism*; D015398:Signal Transduction; D013449:Sulfonamides / Q000494:pharmacology; D014162:Transfection; D014268:Trifluoperazine / Q000494:pharmacology; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D002147:Calmodulin; D018841:HSP90 Heat-Shock Proteins; D011965:Receptors, Glucocorticoid; D013449:Sulfonamides; D010643:Phenoxybenzamine; D014268:Trifluoperazine; D003189:p-Methoxy-N-methylphenethylamine; C017967:W 7; D003907:Dexamethasone; D015500:Chloramphenicol O-Acetyltransferase