E. Giasson et S. Meloche, ROLE OF P70 S6 PROTEIN-KINASE IN ANGIOTENSIN-II-INDUCED PROTEIN-SYNTHESIS IN VASCULAR SMOOTH-MUSCLE CELLS, The Journal of biological chemistry, 270(10), 1995, pp. 5225-5231
Angiotensin II (AII) is a growth factor which induces cellular hypertr
ophy in cultured vascular smooth muscle cells (SMC). To understand the
molecular basis of this action, we have examined the role of the 70-k
Da Se kinases (p70(S6K)) in the hypertrophic response to AII in aortic
SMC. AII potently stimulated the phosphotransferase activity of p70(S
6K), which reached a maximal value at 15 min and persisted for at leas
t 4 h. This response was completely abolished when the cells were incu
bated in the presence of the AT(1)-selective receptor antagonist losar
tan. The enzymatic activation of p70(S6K) was associated with increase
d phosphorylation of the enzyme on serine and threonine residues. The
immunosuppressant drug rapamycin was found to selectively inhibit the
activation of p70(S6K) by AII, but not the activation of mitogen-activ
ated protein kinase or the induction of c-fos mRNA expression. Treatme
nt of aortic SMC with rapamycin also potently inhibited AII-stimulated
protein synthesis with a half-maximal concentration similar to that r
equired for inhibition of p70(S6K). These results provide strong evide
nce that p70(S6K) plays a critical role in the signaling pathways by w
hich AII induces hypertrophy of vascular SMC.