Aldosterone elicits transcriptional responses by binding to the mineralocorticoid receptor (MR), inducing its nuclear translocation and the modulation of gene expression. Aldosterone also stimulates the rapid activation of protein kinase signalling cascades, independently of transcription/translation. Aldosterone induces rapid ERK1/2 MAP kinase signalling and this is stabilised via protein kinase D1 (PKD1) in M1 cortical collecting duct cells (M1-CCD) (1). Here we describe a novel effect of aldosterone on renal cell growth modulated by the ERK1/2 – PKD1 pathway. Aldosterone (10nM) promoted the growth of M1-CCD cells after 48h, as observed using the MTT cell growth assay. This effect was abolished by the inhibition of PKCdelta (20µM Rottlerin) and ERK1/2 (1μM PD98059). The increase in cell growth was due to an aldosterone-mediated increase in the proliferation of M1-CCD cells. The number of viable cells per mm2 was determined by direct counting, after the propagation of cells (initial seeding 5 x104) in the presence of aldosterone (10nM) or in aldosterone-free culture medium for 48h. Aldosterone caused a >2-fold increase in cell count (624.3 ± 98.31, n=10) compared to vehicle-treated (ethanol) control (306.7 ± 54.39, n=10). A stable knockdown of PKD1 was created in M1-CCD cells using a plasmid encoding a PKD1-specific siRNA. No significant increase in cell growth or proliferation was observed in this cell line following aldosterone treatment. Aldosterone (10nM) induced the rapid activation of ERK1/2 with peaks of activation at 2min and 10-30min, followed by sustained activation lasting >120min. Aldosterone promoted the association of PKD1 with ERK1/2 within 2min. The siRNA-mediated PKD1 knockdown cells exhibited only the early transient peaks in ERK1/2 activation (2min and 10-30min), without the sustained phase. Using immunofluorescence and confocal microscopy, we found that aldosterone mediated the subcellular redistribution of ERK1/2 to nuclei at 2min and to cytoplasmic sites proximal to the nuclei at 30min, and this was inhibited in M1-CCD cells suppressed in PKD1 expression. In summary, the PKD1-dependent stabilization of ERK1/2 activation and its subcellular redistribution are required for aldosterone-induced cell proliferation in M1-CCD cells.