HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 291/6/C1308    most recent 00618.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Godeny, M. D. Articles by Sayeski, P. P. Search for Related Content PubMed PubMed Citation Articles by Godeny, M. D. Articles by Sayeski, P. P.

RECEPTORS AND SIGNAL TRANSDUCTION

ERK1/2 regulates ANG II-dependent cell proliferation via cytoplasmic activation of RSK2 and nuclear activation of elk1

Department of Physiology and Functional Genomics, University of Florida College of Medicine, Gainesville, Florida

Submitted 12 December 2005 ; accepted in final form 18 May 2006

In a concurrently submitted article, we show that ANG II-induced ERK1/2 activation is mediated by both c-Src/Yes/Fyn and heterotrimeric G protein/PKC-dependent signaling. Furthermore, we show that heterotrimeric G protein/PKC-activated ERK1/2 is destined for the nucleus while ERK1/2 activated by c-Src/Yes/Fyn-dependent signaling remains in the cytoplasm. Interestingly, both mechanisms of activation are required for maximum ANG II-induced cell proliferation. In this study, we sought to determine the mechanisms by which ERK1/2 facilitate cell proliferation via these distinct nuclear and cytoplasmic events, using cells that were lacking either c-Src/Yes/Fyn or heterotrimeric G protein/PKC-dependent ERK1/2 activation. A loss of c-Src/Yes/Fyn blocked ANG II-dependent RSK2 activation, RSK2 nuclear translocation, serum-response factor (SRF) phosphorylation, a portion of c-fos transcriptional activity and c-Fos phosphorylation. Blocking ANG II-induced heterotrimeric G protein/PKC activity resulted in a loss of ERK1/2 nuclear translocation, elk1 phosphorylation, and the remaining portion of c-fos transcriptional activity not dependent on c-Src/Yes/Fyn. Inhibition of RSK with the potent and selective inhibitor, SL0101, attenuated ANG II-induced cell proliferation, and, in combination with a PKC pseudosubstrate, completely attenuated cell proliferation. Thus we conclude that ERK1/2 mediate ANG II-dependent cell proliferation via distinct cytoplasmic and nuclear signaling events, which are in turn governed by c-Src/Yes/Fyn and heterotrimeric G protein/PKC-dependent signaling, respectively.

SL0101; angiotensin II; ribosomal S6 kinase

This article has been cited by other articles:

				W. Feng, R. E. Brown, C. D. Trung, W. Li, L. Wang, T. Khoury, S. Alrawi, J. Yao, K. Xia, and D. Tan Morphoproteomic Profile of mTOR, Ras/Raf Kinase/ERK, and NF-{kappa}B Pathways in Human Gastric Adenocarcinoma Ann. Clin. Lab. Sci., January 1, 2008; 38(3): 195 - 209. [Abstract] [Full Text] [PDF]

				M. D. Godeny and P. P. Sayeski ANG II-induced cell proliferation is dually mediated by c-Src/Yes/Fyn-regulated ERK1/2 activation in the cytoplasm and PKC{zeta}-controlled ERK1/2 activity within the nucleus Am J Physiol Cell Physiol, December 1, 2006; 291(6): C1297 - C1307. [Abstract] [Full Text] [PDF]