Aldosterone rapidly activates protein kinase D via a mineralocorticoid receptor/EGFR trans-activation pathway in the M1 kidney CCD cell line

Requirement of protein kinase D1 for pathological cardiac remodeling

“…The profibrotic mineralocorticoid, aldosterone, can activate PKD (35), and PKD signaling was recently shown to stimulate aldosterone production in adrenal cells through up-regulation of aldosterone synthase (36). These findings suggest that PKD contributes to a positive-feedback loop that promotes cardiac fibrosis.…”

Estrogen inhibits chloride secretion caused by cholera and Escherichia coli enterotoxins in female rat distal colon

“…Recent evidence has also suggested EGFR can be transactivated by steroid hormones in a nongenomic fashion [26][27][28][29]. To determine if transactivation of the EGFR plays a role in antisecretory effect of 17-estradiol, we examined the effects of the EGFR inhibitor, tyrphostin -1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 …”

Aldosterone as a renal growth factor

“…Modulation of cell growth by aldosterone; whether it is a metabolic stimulation (hypertrophy) or the stimulation of cell proliferation (hyperplasia) requires co-ordination of rapid signalling and transcriptional changes. The activation of several signalling cascades by aldosterone has been identified in cells derived from the distal nephron including the PKC [12], PKD1 [13] and ERK1/2 mitogen activated protein (MAP) kinase [14] cascades. A number of the signalling cascades rapidly activated by aldosterone such as the Ca 2+ -dependent PKC isoforms and ERK1/2 also promote cell proliferation in response to mitogenic agonists.…”

“…PKD family isoforms are in some way responsible for stabilizing the initial growth factor-stimulated ERK1/2 activation [20]. The MR-dependent autophosphorylation of protein kinase D occurs within 5 min of treating CCD cells with aldosterone [13]. The rapid PKD activation coincides temporally with initial ERK1/2 activation in these cells.…”

“…The rapid PKD activation coincides temporally with initial ERK1/2 activation in these cells. The activation of both PKD and ERK1/2 by aldosterone are dependent on the transactivation and phosphorylation of the EGF receptor (EGFR) by c-Src tyrosine kinase [13,21,22]. In wild-type CCD cells aldosterone stimulates ERK1/2 activation which remains detectable 2 hours after treatment.…”