AJP - Heart Add DOIs to your references at manuscript stage!
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Heart Circ Physiol 278: H1537-H1544, 2000;
0363-6135/00 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
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 Web of Science (28)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kraiss, L. W.
Right arrow Articles by Zimmerman, G. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kraiss, L. W.
Right arrow Articles by Zimmerman, G. A.
Vol. 278, Issue 5, H1537-H1544, May 2000

Fluid flow activates a regulator of translation, p70/p85 S6 kinase, in human endothelial cells

Larry W. Kraiss1,2,3, Andrew S. Weyrich2,4, Neal M. Alto1, Dan A. Dixon2, Tina M. Ennis1,2, Vijayanand Modur5, Thomas M. McIntyre2,4,5, Stephen M. Prescott2,4,6, and Guy A. Zimmerman2,4

1 Division of Vascular Surgery, Department of Surgery; 2 Program in Human Molecular Biology and Genetics, Eccles Institute of Human Genetics; 3 Surgical Service, Salt Lake Veterans Affairs Medical Center; and Departments of 4 Internal Medicine, 5 Pathology, and 6 Biochemistry, University of Utah, Salt Lake City, Utah 84112

Cellular phenotype is determined not only by genetic transcription but also by subsequent translation of mRNA into protein. Extracellular signals trigger intracellular pathways that distinctly activate translation. The 70/85-kDa S6 kinase (pp70S6k) is a central enzyme in the signal-dependent control of translation, but its regulation in endothelial cells is largely unknown. Here we show that fluid flow (in the absence of an exogenous mitogen) as well as humoral agonists activate endothelial pp70S6k. Rapamycin, an inhibitor of the mammalian target of rapamycin (mTOR), and wortmannin, a phosphatidylinositol 3-kinase inhibitor, blocked flow-induced pp70S6k activation; FK-506, a rapamycin analog with minimal mTOR inhibitory activity, and PD-98059, an inhibitor of the flow-sensitive mitogen-activated protein kinase pathway, had no effect. Synthesis of Bcl-3, a protein whose translation is controlled by an mTOR-dependent pathway, was induced by flow and inhibited by rapamycin and wortmannin. Transcriptional blockade did not abolish the flow-induced upregulation of Bcl-3. Fluid forces may therefore modify endothelial phenotype by specifically regulating translation of certain mRNA transcripts into protein.

signal transduction; hemorheology; rapamycin; phosphatidylinositol 3-kinase; phenotype


This article has been cited by other articles:


Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
W. Li and B. E. Sumpio
Strain-induced vascular endothelial cell proliferation requires PI3K-dependent mTOR-4E-BP1 signal pathway
Am J Physiol Heart Circ Physiol, April 1, 2005; 288(4): H1591 - H1597.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
T. A. Hornberger, D. D. Armstrong, T. J. Koh, T. J. Burkholder, and K. A. Esser
Intracellular signaling specificity in response to uniaxial vs. multiaxial stretch: implications for mechanotransduction
Am J Physiol Cell Physiol, January 1, 2005; 288(1): C185 - C194.
[Abstract] [Full Text] [PDF]

Home page
 JEMHome page
C. C. Yost, M. M. Denis, S. Lindemann, F. J. Rubner, G. K. Marathe, M. Buerke, T. M. McIntyre, A. S. Weyrich, and G. A. Zimmerman
Activated Polymorphonuclear Leukocytes Rapidly Synthesize Retinoic Acid Receptor-{alpha}: A Mechanism for Translational Control of Transcriptional Events
J. Exp. Med., September 7, 2004; 200(5): 671 - 680.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
B. Ge, O. Li, P. Wilder, A. Rizzino, and T. W. McKeithan
NF-{kappa}B Regulates BCL3 Transcription in T Lymphocytes Through an Intronic Enhancer
J. Immunol., October 15, 2003; 171(8): 4210 - 4218.
[Abstract] [Full Text] [PDF]

Home page
 VASC ENDOVASCULAR SURGHome page
J. J. Paszkowiak and A. Dardik
Arterial Wall Shear Stress: Observations from the Bench to the Bedside
Vascular and Endovascular Surgery, January 1, 2003; 37(1): 47 - 57.
[Abstract] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
Y. D. Li, E. R. Block, and J. M. Patel
Activation of multiple signaling modules is critical in angiotensin IV-induced lung endothelial cell proliferation
Am J Physiol Lung Cell Mol Physiol, October 1, 2002; 283(4): L707 - L716.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
K. Bove, P. Neumann, N. Gertzberg, and A. Johnson
Role of ecNOS-derived NO in mediating TNF-induced endothelial barrier dysfunction
Am J Physiol Lung Cell Mol Physiol, May 1, 2001; 280(5): L914 - L922.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
O. J. Shah, J. A. Iniguez-Lluhi, A. Romanelli, S. R. Kimball, and L. S. Jefferson
The Activated Glucocorticoid Receptor Modulates Presumptive Autoregulation of Ribosomal Protein S6 Protein Kinase, p70 S6K
J. Biol. Chem., January 18, 2002; 277(4): 2525 - 2533.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online