Intracellular signaling pathways confer specificity of transactivation by mineralocorticoid and glucocorticoid receptors

Endocrinology
S S Lim-Tio, Peter J Fuller

Abstract

The glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR) bind similar ligands and target genes in vitro yet have distinct roles in vivo. With a single exception, known mechanisms conferring specificity have been limited to prereceptor mechanisms. These alone cannot account for specificity, particularly at a transcriptional level. These studies aimed to determine whether receptor-specific transcriptional regulation via physiological modulators of cellular signaling pathways, and MR-, as well as GR-specific interactions, could be demonstrated. By comparing modulation of GR- and MR-mediated transactivation in renal LLC-PK1 cells, we have identified several activators of intracellular signaling pathways that discriminate between the GR and the MR and demonstrate that differential regulation occurs at relatively specific points in the signaling pathway. The phosphatase inhibitor, okadaic acid, and the protein kinase G activator, sodium nitroprusside, stimulate only GR-mediated transactivation, in contrast to modulators of other protein kinase pathways that act in parallel on both receptors. The GR-specific effect of okadaic acid is observed only at doses where both phosphatases 1 and 2A are inhibited. MR-specific mod...Continue Reading

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Citations

Nov 13, 2001·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·E VreugdenhilN A Datson
May 12, 2004·Molecular and Cellular Endocrinology·Fraser M RogersonPeter J Fuller
Jan 28, 2010·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Claudia GrossmannMichael Gekle
Feb 24, 2001·American Journal of Physiology. Renal Physiology·N Farman, M E Rafestin-Oblin
Apr 12, 2016·Journal of Animal Science·C R Ralph, A J Tilbrook
Dec 14, 1999·The Journal of Biological Chemistry·F M RogersonP J Fuller
Apr 12, 2000·Kidney International·P J FullerF E Brennan
Apr 12, 2000·Kidney International·C DelcayreV Robert
Apr 12, 2000·Kidney International·A CrocollA C Cato

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