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Acetophenones, Active Transport, Cell Nucleus, Aldosterone, Aldosterone Antagonists, Animals, Benzopyrans, Cell Line, Cell Proliferation, Cytoplasm, Enzyme Activation, Epithelial Cells, Extracellular Signal-Regulated MAP Kinases, Flavonoids, Kidney Cortex, Kidney Tubules, Collecting, Mice, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, Models, Biological, Phosphorylation, Protein Binding, Protein Kinase C-delta, Protein Kinase Inhibitors, Receptor, Epidermal Growth Factor, Receptors, Mineralocorticoid, Signal Transduction, Spironolactone, TRPP Cation Channels, Tyrphostins


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Aldosterone elicits transcriptional responses in target tissues and also rapidly stimulates the activation of protein kinase signalling cascades independently of de novo protein synthesis. Here we investigated aldosterone-induced cell proliferation and extra-cellular regulated kinase 1 and 2 (ERK1/2) mitogen activated protein (MAP) kinase signalling in the M1 cortical collecting duct cell line (M1-CCD). Aldosterone promoted the proliferative growth of M1-CCD cells, an effect that was protein kinase D1 (PKD1), PKCdelta and ERK1/2-dependent. Aldosterone induced the rapid activation of ERK1/2 with peaks of activation at 2 and 10 to 30 min after hormone treatment followed by sustained activation lasting beyond 120 min. M1-CCD cells suppressed in PKD1 expression exhibited only the early, transient peaks in ERK1/2 activation without the sustained phase. Aldosterone stimulated the physical association of PKD1 with ERK1/2 within 2 min of treatment. The mineralocorticoid receptor (MR) antagonist RU28318 inhibited the early and late phases of aldosterone-induced ERK1/2 activation, and also aldosterone-induced proliferative cell growth. Aldosterone induced the sub-cellular redistribution of ERK1/2 to the nuclei at 2 min and to cytoplasmic sites, proximal to the nuclei after 30 min. This sub-cellular distribution of ERK1/2 was inhibited in cells suppressed in the expression of PKD1.


Medical Molecular Biology | Medical Sciences


McEneaney V, Dooley R, Harvey BJ, Thomas W. Protein kinase D stabilizes aldosterone-induced ERK1/2 MAP kinase activation in M1 renal cortical collecting duct cells to promote cell proliferation. Journal of Steroid Biochemistry and Molecular Biology. 2010;118(1-2):18-28.

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