The University of Southampton
University of Southampton Institutional Repository

ANG II activates effectors of mTOR via PI3-K signaling in human coronary smooth muscle cells

Hafizi, Sassan, Wang, Xuemin, Chester, Adrian H., Yacoub, Magdi H. and Proud, Christopher G. (2004) ANG II activates effectors of mTOR via PI3-K signaling in human coronary smooth muscle cells American Journal of Physiology: Heart and Circulatory Physiology, 287, H1232-H1238. (doi:10.1152/ajpheart.00040.2004).

Record type: Article

Abstract

We have previously shown that the vasoconstrictive peptide angiotensin II (ANG II) is a hypertrophic agent for human coronary artery smooth muscle cells (cSMCs), which suggests that it plays a role in vascular wall thickening. The present study investigated the intracellular signal transduction pathways involved in the growth response of cSMCs to ANG II. The stimulation of protein synthesis by ANG II in cSMCs was blocked by the immunosuppressant rapamycin, which is an inhibitor of the mammalian target of rapamycin (mTOR) signaling pathway that includes the 70-kDa S6 kinase (p70S6k) and plays a key role in cell growth. The inhibitory effect of rapamycin was reversed by a molar excess of FK506; this indicates that both agents act through the common 12-kDa immunophilin FK506-binding protein. ANG II caused a rapid and sustained activation of p70S6k activity that paralleled its phosphorylation, and both processes were blocked by rapamycin. In addition, both of the phosphatidylinositol 3-kinase inhibitors wortmannin and LY-294002 abolished the ANG II-induced increase in protein synthesis, and wortmannin also blocked p70S6k phosphorylation. Furthermore, ANG II triggered dissociation of the translation initiation factor, eukaryotic initiation factor-4E, from its regulatory binding protein 4E-BP1, which was also inhibited by rapamycin and wortmannin. In conclusion, we have shown that ANG II activates components of the rapamycin-sensitive mTOR signaling pathway in human cSMCs and involves activation of phosphatidylinositol 3-kinase, p70S6k, and eukaryotic initiation factor-4E, which leads to activation of protein synthesis. These signaling mechanisms may mediate the growth-promoting effect of ANG II in human cSMCs.

Full text not available from this repository.

More information

Published date: 1 September 2004
Keywords: mammalian target of rapamycin, S6 kinase, phosphatidylinositol 3-kinase, angiotensin II

Identifiers

Local EPrints ID: 56001
URI: http://eprints.soton.ac.uk/id/eprint/56001
ISSN: 0363-6135
PURE UUID: 05fd70ab-5e9b-4b0b-9e63-c9c37c0288eb

Catalogue record

Date deposited: 07 Aug 2008
Last modified: 17 Jul 2017 14:31

Export record

Altmetrics

Contributors

Author: Sassan Hafizi
Author: Xuemin Wang
Author: Adrian H. Chester
Author: Magdi H. Yacoub
Author: Christopher G. Proud

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×