Aldosterone promotes Na⁺ absorption and K⁺ secretion in target tissues such as the epithelia of the distal colon and distal nephron. The osmotic movement of water concurrent with Na⁺ absorption means that the net effect of aldosterone release on the whole body is to increase extracellular fluid volume and consequently raise blood pressure [1]. The cytoplasmic mineralocorticoid receptor(MR) acts as a ligand-dependent transcription factor [2]. However, the earliest investigation of rapid physiological responses to aldosterone describes the hormone’s effects on Na⁺ and K⁺ excretion into the urine within 5 min following its intra-arterial administration [3]. Rapid signaling responses have been observed following aldosterone treatment, including the activation of protein kinase signaling cascades and a rise in [Ca²⁺]_I [4,5]. The rapid autophosphorylation and activation of the novel Serine/Threonine protein kinase Protein kinase D1 (PKD1) in the murine M1 renal cortical collecting duct (M1-CCD) cell line within 5 min of aldosterone (10 nM) treatment (n=6) was demonstrated. M1-CCD cells were routinely propagated in the presence of dexamethasone (5 μM). It was established that dexamethasone withdrawal resulted in a reversible suppression of MR expression by these cells (n=4) that blocked the autophosphorylation of PKD1 at Sre916 in response to aldosterone (n=6). It was demonstrated that the epidermal growth factor receptor (EGFR) inhibitor Tyrphostin AG1478 (30 nM) inhibited the autophosphorylation of PKD1 (n=4). It was further established that EGFR became phosphorylated at Ser845 in response to aldosterone and that both this phosphorylation event and the autophosphorylation of PKD1 were sensitive to the c-Src kinase family inhibitor PP2 (100 nM) (n=4). Aldosterone treatment promotes the association of c-Src with Heat shock protein 84 (Hsp84) the murine homologue of human Hsp90. It was demonstrated that the Hsp90 antagonist 17-allylaminogeldanamycin (17-AAG) (5 μM) inhibitor both the Src tyrosine kinase-dependent phosphorylation of EGFR and also the autophosphorylation of PKD1 in response to aldosterone (n=4). An M1-CCD derived cell line that was stably suppressed in its PKD1 expression failed to translocate green fluorescent protein tagged epithelial sodium channel subunits to its apical surface following aldosterone treatment. Consequently the aldosterone-induced activation of PKD1 has a significant role in priming the physiological responses stimulated by this hormone.