Effects of angiotensin II and adrenocorticotropic hormone on myristoylated alanine-rich C-kinase substrate phosphorylation in glomerulosa cells.
Angiotensin II (AngII) is thought to stimulate aldosterone secretion from bovine adrenal glomerulosa cells in part via activation of protein kinase C (PKC), while adrenocorticotropic hormone (ACTH) functions through increases in intracellular cAMP levels and calcium influx. Rather than using invasive homogenization techniques as in previous studies, we chose to monitor PKC activity in intact glomerulosa cells in situ by measuring the phosphorylation of the endogenous PKC substrate, myristoylated alanine-rich C-kinase substrate (MARCKS). AngII enhanced MARCKS phosphorylation in a rapid, sustained manner; whereas ACTH induced a rapid and sustained inhibition of MARCKS phosphorylation. Studies using pharmacological agents to mimic various signals indicated that the AngII-induced MARCKS phosphorylation was due to PKC activation, and the ACTH-elicited decrease was mediated by increases in calcium influx rather than cAMP production. We propose that changes in the phosphorylation state of MARCKS, an actin-binding protein, may contribute to cytoskeletal rearrangements involved in steroidogenesis.
Betancourt-Calle
S
S
Department of Medicine, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta 30912-2630, USA.
Bollag
W B
WB
Jung
E M
EM
Calle
R A
RA
Rasmussen
H
H
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000450:Aldosterone / Q000378:metabolism; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism / Q000502:physiology; D011506:Proteins / Q000378:metabolism*; D015384:Zona Glomerulosa / Q000166:cytology* / Q000378:metabolism
D002120:Calcium Channel Agonists; D047908:Intracellular Signaling Peptides and Proteins; C000619710:MARCKS protein, human; D008565:Membrane Proteins; D011506:Proteins; D000804:Angiotensin II; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D005576:Colforsin; D000450:Aldosterone; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D000324:Adrenocorticotropic Hormone; D011493:Protein Kinase C