AJP - Heart Watch the video to see how APS reaches out to developing nations.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Heart Circ Physiol 286: H1881-H1888, 2004. First published January 2, 2004; doi:10.1152/ajpheart.00786.2003
0363-6135/04 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
286/5/H1881    most recent
00786.2003v2
00786.2003v1
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 ISI 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 ISI Web of Science (15)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Cho, C.-H.
Right arrow Articles by Koh, G. Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cho, C.-H.
Right arrow Articles by Koh, G. Y.

Localization of VEGFR-2 and PLD2 in endothelial caveolae is involved in VEGF-induced phosphorylation of MEK and ERK

Chung-Hyun Cho, Chang Sup Lee, Mikyung Chang, Il-Ho Jang, Soo Jin Kim, Inhwan Hwang, Sung Ho Ryu, Chin O. Lee, and Gou Young Koh

National Creative Research Initiatives Center for Endothelial Cells and Division of Molecular and Life Sciences, Pohang University of Science and Technology, Pohang, 790-784, Republic of Korea

Submitted 15 August 2003 ; accepted in final form 30 December 2003

To clarify the role of caveolae in VEGF/VEGF receptor-2 (VEGFR-2)-mediated signaling cascades, primary cultured human umbilical vein endothelial cells (HUVECs) were fractionated to isolate caveolae-enriched cell membranes. Interestingly, VEGFR-2, phospholipase D2 (PLD2), and Ras were enriched in caveolae-enriched fractions. Moreover, VEGF increased PLD activity in a time- and dose-dependent manner in HUVECs, whereas a ligand specific for VEGFR-1 placental growth factor did not change PLD activity. A PLD inhibitor, 1-butanol, almost completely suppressed VEGF-induced ERK phosphorylation and cellular proliferation, whereas the negative control for 1-butanol, 3-butanol, did not produce significant changes. Addition of phosphatidic acid negated the 1-butanol-induced suppression. Pharmacological analyses using several inhibitors indicated that PKC-{delta} regulates the VEGF-induced activation of PLD/ERK. Thus PLD2 could be involved in MEK/ERK signaling cascades that are induced by the VEGF/VEGFR-2/PKC-{delta} pathway in endothelial cells. Pretreatment with the cholesterol depletion agent methyl-{beta}-cyclodextrin (M{beta}CD) almost completely disassembled caveolar structures, whereas the addition of cholesterol to M{beta}CD-treated cells restored caveolar structures. Pretreatment with M{beta}CD largely abolished phosphorylation of MEK/ERK by VEGF, whereas the addition of cholesterol restored VEGF-induced MEK/ERK phosphorylations. These results indicate that intact caveolae are required for the VEGF/VEGFR-2-mediated MEK/ERK signaling cascade.

caveolin-1; protein kinase C-{delta}; signaling; vascular endothelial growth factor; phospholipase D


Address for reprint requests and other correspondence: G. Y. Koh, National Creative Research Initiatives Center for Endothelial Cells, Division of Molecular and Life Sciences, Pohang Univ. of Science and Technology, San 31, Hyoja-Dong, Pohang, 790-784, Republic of Korea (E-mail: gykoh{at}postech.ac.kr).




This article has been cited by other articles:


Home page
 J. Lipid Res.Home page
P. Mukherjee, A. C. Faber, L. M. Shelton, R. C. Baek, T. C. Chiles, and T. N. Seyfried
Thematic Review Series: Sphingolipids. Ganglioside GM3 suppresses the proangiogenic effects of vascular endothelial growth factor and ganglioside GD1a
J. Lipid Res., May 1, 2008; 49(5): 929 - 938.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
R. Gosens, G. Dueck, W. T. Gerthoffer, H. Unruh, J. Zaagsma, H. Meurs, and A. J. Halayko
p42/p44 MAP kinase activation is localized to caveolae-free membrane domains in airway smooth muscle
Am J Physiol Lung Cell Mol Physiol, May 1, 2007; 292(5): L1163 - L1172.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
W. Chen, D. B. Jump, W. J. Esselman, and J. V. Busik
Inhibition of Cytokine Signaling in Human Retinal Endothelial Cells through Modification of Caveolae/Lipid Rafts by Docosahexaenoic Acid
Invest. Ophthalmol. Vis. Sci., January 1, 2007; 48(1): 18 - 26.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
A. C. S. Sobke, D. Selimovic, V. Orlova, M. Hassan, T. Chavakis, A. N. Athanasopoulos, U. Schubert, M. Hussain, G. Thiel, K. T. Preissner, et al.
The extracellular adherence protein from Staphylococcus aureus abrogates angiogenic responses of endothelial cells by blocking Ras activation
FASEB J, December 1, 2006; 20(14): 2621 - 2623.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
C. Ballard-Croft, A. C. Locklar, G. Kristo, and R. D. Lasley
Regional myocardial ischemia-induced activation of MAPKs is associated with subcellular redistribution of caveolin and cholesterol
Am J Physiol Heart Circ Physiol, August 1, 2006; 291(2): H658 - H667.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
M. Li, K.-R. Chiou, A. Bugayenko, K. Irani, and D. A. Kass
Reduced Wall Compliance Suppresses Akt-Dependent Apoptosis Protection Stimulated by Pulse Perfusion
Circ. Res., September 16, 2005; 97(6): 587 - 595.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2004 by the American Physiological Society.