Am J Physiol Cell Physiol Journal of Applied Physiology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Am J Physiol Cell Physiol (July 30, 2003). doi:10.1152/ajpcell.00075.2003
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
285/6/C1437    most recent
00075.2003v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Rocic, P.
Right arrow Articles by Lucchesi, P. A
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rocic, P.
Right arrow Articles by Lucchesi, P. A
Submitted on February 25, 2003
Accepted on July 26, 2003

A Role for PYK2 in Angiotensin II-Dependent Regulation of the PHAS- 1/eIF4E Complex by Multiple Signaling Cascades in Vascular Smooth Muscle

Petra Rocic1, Hanjoong Jo2, and Pamela A Lucchesi1*

1 Physiology and Biophysics, University of Alabama Birmingham, Birmingham, AL, USA
2 Coulter Department of Biomedical Engineering, Georgia Tech and Emory University, Atlanta, GA, none

* To whom correspondence should be addressed. E-mail: lucchesi{at}physiology.uab.edu.

The regulation of the PHAS-1/eIF4E complex is the rate-limiting step in the initiation of protein synthesis. This study characterized the upstream signaling pathways that mediate Ang II-dependent phosphorylation of PHAS-1 and eIF4E in vascular smooth muscle. Ang II-dependent PHAS-1 phosphorylation was maximal at 10 minutes (2.47 ± 0.3 fold vs. control). This effect was completely blocked by the specific inhibitors of phosphatidylinositol 3-kinase (PI3-kinase, LY294002), of p70S6 kinase (rapamycin) and of the extracellular signal-regulated kinase 1/2 (ERK1/2) (U0126) or by a recombinant adenovirus encoding dominant negative Akt. PHAS-1 phosphorylation was followed by dissociation of eIF4E. Increased Ang II-induced eIF4E phosphorylation was observed at 45 minutes (2.63 ± 0.5 fold vs. control), was maximal at 90 minutes (3.38 ± 0.3 fold vs. control) and sustained at 2 hours. This effect was blocked by inhibitors of the ERK1/2 and p38 mitogen-activated protein (MAP) kinase pathways, but not by PI3-kinase inhibition, and was dependent upon PKC, intracellular Ca2+, and tyrosine kinases. Downregulation of PYK2 by antisense oligonucleotides lead to a complete inhibition of both PHAS-1 and eIF4E phosphorylation in response to Ang II. Therefore, PYK2 represents a proximal signaling intermediate that regulates Ang II-induced VSMC protein synthesis via regulation of the PHAS-1/eIF4E complex.




This article has been cited by other articles:


Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
Z. Ying, F. R.C. Giachini, R. C. Tostes, and R. C. Webb
PYK2/PDZ-RhoGEF Links Ca2+ Signaling to RhoA
Arterioscler Thromb Vasc Biol, October 1, 2009; 29(10): 1657 - 1663.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
R. Reed, B. Potter, E. Smith, R. Jadhav, P. Villalta, H. Jo, and P. Rocic
Redox-sensitive Akt and Src regulate coronary collateral growth in metabolic syndrome
Am J Physiol Heart Circ Physiol, June 1, 2009; 296(6): H1811 - H1821.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
P. K. Mehta and K. K. Griendling
Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system
Am J Physiol Cell Physiol, January 1, 2007; 292(1): C82 - C97.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 1976 by the American Physiological Society.