10779/rcsi.10786493.v1
Victoria McEneaney
Victoria
McEneaney
Ruth Dooley
Ruth
Dooley
Brian J. Harvey
Brian J.
Harvey
Warren Thomas
Warren
Thomas
Protein kinase D stabilizes aldosterone-induced ERK1/2 MAP kinase activation in M1 renal cortical collecting duct cells to promote cell proliferation.
Royal College of Surgeons in Ireland
2019
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
Molecular Medicine
2019-11-22 16:39:08
Journal contribution
https://repository.rcsi.com/articles/journal_contribution/Protein_kinase_D_stabilizes_aldosterone-induced_ERK1_2_MAP_kinase_activation_in_M1_renal_cortical_collecting_duct_cells_to_promote_cell_proliferation_/10786493
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.