title: Protein kinase D stabilizes aldosterone-induced ERK1/2 MAP kinase activation in M1 renal cortical collecting duct cells to promote cell proliferation.
abstract: 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.
authors.affiliation: Department of Molecular Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland.
authors.forename: Victoria
authors.initials: V
authors.lastname: McEneaney
authors.forename: Ruth
authors.initials: R
authors.lastname: Dooley
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Harvey
authors.forename: Warren
authors.initials: W
authors.lastname: Thomas
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D003593:Cytoplasm / Q000378:metabolism; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D007672:Kidney Cortex / Q000166:cytology*; D007685:Kidney Tubules, Collecting / Q000166:cytology*; D051379:Mice; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D008954:Models, Biological; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D051745:Protein Kinase C-delta / Q000037:antagonists & inhibitors / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011799:Quinazolines; D018161:Receptors, Mineralocorticoid / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013148:Spironolactone / Q000031:analogs & derivatives / Q000494:pharmacology; D050396:TRPP Cation Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020032:Tyrphostins / Q000494:pharmacology
chemical_list: D000098:Acetophenones; D000450:Aldosterone; D001578:Benzopyrans; D066246:ErbB Receptors; D048049:Extracellular Signal-Regulated MAP Kinases; D005419:Flavonoids; D000451:Mineralocorticoid Receptor Antagonists; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D051745:Protein Kinase C-delta; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D018161:Receptors, Mineralocorticoid; D013148:Spironolactone; D050396:TRPP Cation Channels; D020032:Tyrphostins; C101044:RTKI cpd; C041006:RU 28318; C085746:rottlerin; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one