title: Elevated K(+) induces myristoylated alanine-rich C-kinase substrate phosphorylation and phospholipase D activation in glomerulosa cells.
abstract: Elevated extracellular potassium concentrations ([K(+)](e)) are known to stimulate aldosterone secretion from adrenal glomerulosa cells in vivo and in vitro. The mechanism is thought to involve depolarization-elicited activation of voltage-dependent calcium channels and an increase in calcium influx. Until now protein kinase C (PKC) was thought not to play a role in the steroidogenic response to elevated [K(+)](e). In this report, we provide evidence in bovine adrenal glomerulosa cells to suggest that elevated [K(+)](e) increases PKC activity, as shown by an enhancement in the phosphorylation of myristoylated alanine-rich C-kinase substrate (MARCKS). Elevated [K(+)](e)-induced MARCKS phosphorylation was delayed and transient and was not the result of a local production of angiotensin II (AngII). MARCKS phosphorylation in response to elevated [K(+)](e) was not accompanied by phosphoinositide hydrolysis but was inhibited by a selective PKC inhibitor. Elevated [K(+)](e) also activated phospholipase D (PLD) in a delayed but sustained manner. We propose that the observed PLD activation mediates the elevated [K(+)](e)-induced MARCKS phosphorylation via PKC, although other factors may modulate this phosphorylation event.
authors.affiliation: Program in Cell Signaling, Department of Medicine, Institute of Molecular Medicine and Genetics, Medical College of Georgia, 1120 15th Street, Augusta, GA 30912-2630, USA.
authors.forename: S
authors.initials: S
authors.lastname: Betancourt-Calle
authors.forename: E M
authors.initials: EM
authors.lastname: Jung
authors.forename: S
authors.initials: S
authors.lastname: White
authors.forename: S
authors.initials: S
authors.lastname: Ray
authors.forename: X
authors.initials: X
authors.lastname: Zheng
authors.forename: R A
authors.initials: RA
authors.lastname: Calle
authors.forename: W B
authors.initials: WB
authors.lastname: Bollag
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D004075:Diglycerides / Q000032:analysis; D004789:Enzyme Activation / Q000187:drug effects; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D010716:Phosphatidylinositols / Q000032:analysis; D010739:Phospholipase D / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D010750:Phosphoproteins / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011188:Potassium / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism / Q000502:physiology; D015290:Second Messenger Systems; D015384:Zona Glomerulosa / Q000166:cytology*
chemical_list: D004075:Diglycerides; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D010716:Phosphatidylinositols; D010750:Phosphoproteins; D000804:Angiotensin II; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D011493:Protein Kinase C; D010739:Phospholipase D; D011188:Potassium