Angiotensin II induces phosphorylation of eukaryotic protein synthesis initiation factor 4E in vascular smooth muscle cells.
Angiotensin II has been shown to induce hypertrophy of cultured vascular smooth muscle cells (VSMC). To understand the mechanisms of induction of the hypertrophy, we studied its effect on the phosphorylation state of eIF-4E, a rate-limiting eukaryotic protein synthesis initiation factor whose activity has been shown to be regulated by phosphorylation. Angiotensin II induced a 2-3-fold increase in the phosphorylation of eIF-4E in VSMC. The stimulation of phosphorylation was apparent at 20 min and persisted for at least 12 h. Phosphoamino acid analysis revealed that serine is the major residue of eIF-4E phosphorylated by angiotensin II. Staurosporine and calphostin C, two potent inhibitors of the serine/threonine protein kinase, protein kinase C, significantly attenuated the angiotensin II-induced eIF-4E phosphorylation. Staurosporine and calphostin C also blunted the angiotensin II-stimulated protein synthesis. Together, these observations indicate that angiotensin II induces phosphorylation of eIF-4E in a protein kinase C-dependent manner and suggest that this pathway may play an important role in the mechanism by which angiotensin II causes hypertrophy of VSMC.
Rao
G N
GN
Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia 30322.
Griendling
K K
KK
Frederickson
R M
RM
Sonenberg
N
N
Alexander
R W
RW
D000470:Alkaloids / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D039561:Eukaryotic Initiation Factor-4E; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D010448:Peptide Initiation Factors / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000470:Alkaloids; D039561:Eukaryotic Initiation Factor-4E; D010448:Peptide Initiation Factors; D000804:Angiotensin II; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate