![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 10, Issue 10, 3401-3407, October 1999
*Boston University, School of Medicine, Boston, Massachusetts
02028; and FLK-1/vascular endothelial growth factor receptor 2 (VEGFR-2) is one of the receptors for VEGF. In this study we examined the effect of cell density on activation of VEGFR-2. VEGF induces only
very slight tyrosine phosphorylation of VEGFR-2 in confluent (95-100%
confluent) pig aortic endothelial (PAE) cells. In contrast, robust
VEGF-dependent tyrosine phosphorylation of VEGFR-2 was observed in
cells plated in sparse culture conditions (60-65% confluent). A
similar cell density-dependent phenomenon was observed in different
endothelial cells but not in NIH-3T3 fibroblast cells expressing
VEGFR-2. Stimulating cells with high concentrations of VEGF or
replacing the extracellular domain of VEGFR-2 with that of the
colony-stimulating factor 1 receptor did not alleviate the sensitivity
of VEGFR-2 to cell density, indicating that the confluent cells were
probably not secreting an antagonist to VEGF. Furthermore, in PAE
cells, ectopically introduced platelet-derived growth factor Schepens Eye Research Institute, Harvard
Medical School, Boston, Massachusetts 02114
receptor could be activated at both high and low cell density
conditions, indicating that the density effect was not universal for
all receptor tyrosine kinases expressed in endothelial cells. In
addition to lowering the density of cells, removing divalent cations
from the medium of confluent cells potentiated VEGFR-2 phosphorylation
in response to VEGF. These findings suggested that cell-cell contact
may be playing a role in regulating the activation of VEGFR-2. To this
end, pretreatment of confluent PAE cells with a neutralizing
anti-cadherin-5 antibody potentiated the response of VEGFR-2 to VEGF.
Our data demonstrate that endothelial cell density plays a critical
role in regulating VEGFR-2 activity, and that the underlying mechanism
appears to involve cadherin-5.
Corresponding author. E-mail address:
kazlauskas{at}vision.eri.harvard.edu.
This article has been cited by other articles:
|
|
 |
|
  D. Vestweber VE-Cadherin: The Major Endothelial Adhesion Molecule Controlling Cellular Junctions and Blood Vessel Formation Arterioscler. Thromb. Vasc. Biol., February 1, 2008; 28(2): 223 - 232. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Lei, A. Venkatakrishnan, S. Yu, and A. Kazlauskas Protein Kinase A-dependent Translocation of Hsp90{alpha} Impairs Endothelial Nitric-oxide Synthase Activity in High Glucose and Diabetes J. Biol. Chem., March 30, 2007; 282(13): 9364 - 9371. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Okada, M. Lopez-Lago, and F. G. Giancotti Merlin/NF-2 mediates contact inhibition of growth by suppressing recruitment of Rac to the plasma membrane J. Cell Biol., October 24, 2005; 171(2): 361 - 371. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Podar and K. C. Anderson The pathophysiologic role of VEGF in hematologic malignancies: therapeutic implications Blood, February 15, 2005; 105(4): 1383 - 1395. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Iurlaro, F. Demontis, M. Corada, L. Zanetta, C. Drake, M. Gariboldi, S. Peiro, A. Cano, P. Navarro, A. Cattelino, et al. VE-Cadherin Expression and Clustering Maintain Low Levels of Survivin in Endothelial Cells Am. J. Pathol., July 1, 2004; 165(1): 181 - 189. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Lei, G. Romeo, and A. Kazlauskas Heat Shock Protein 90{alpha}-Dependent Translocation of Annexin II to the Surface of Endothelial Cells Modulates Plasmin Activity in the Diabetic Rat Aorta Circ. Res., April 16, 2004; 94(7): 902 - 909. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Mariner, M. A. Davis, and A. B. Reynolds EGFR signaling to p120-catenin through phosphorylation at Y228 J. Cell Sci., March 15, 2004; 117(8): 1339 - 1350. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ding, T. Merkulova-Rainon, Z. C. Han, and G. Tobelem HGF receptor up-regulation contributes to the angiogenic phenotype of human endothelial cells and promotes angiogenesis in vitro Blood, June 15, 2003; 101(12): 4816 - 4822. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. G. Lampugnani, A. Zanetti, M. Corada, T. Takahashi, G. Balconi, F. Breviario, F. Orsenigo, A. Cattelino, R. Kemler, T. O. Daniel, et al. Contact inhibition of VEGF-induced proliferation requires vascular endothelial cadherin, {beta}-catenin, and the phosphatase DEP-1/CD148 J. Cell Biol., May 26, 2003; 161(4): 793 - 804. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Burkart, B. Samii, S. Corvera, and H. S. Shpetner Regulation of the SHP-2 Tyrosine Phosphatase by a Novel Cholesterol- and Cell Confluence-dependent Mechanism J. Biol. Chem., May 9, 2003; 278(20): 18360 - 18367. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. D. Meyer, C. Latz, and N. Rahimi Recruitment and Activation of Phospholipase Cgamma 1 by Vascular Endothelial Growth Factor Receptor-2 Are Required for Tubulogenesis and Differentiation of Endothelial Cells J. Biol. Chem., April 25, 2003; 278(18): 16347 - 16355. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. L. C. Albuquerque and A. S. Flozak Wound Closure in Sheared Endothelial Cells Is Enhanced by Modulation of Vascular Endothelial-Cadherin Expression and Localization Experimental Biology and Medicine, December 1, 2002; 227(11): 1006 - 1016. [Abstract] [Full Text]
|
|
|
|
|
|
A. Zanetti, M. G. Lampugnani, G. Balconi, F. Breviario, M. Corada, L. Lanfrancone, and E. Dejana Vascular Endothelial Growth Factor Induces Shc Association With Vascular Endothelial Cadherin: A Potential Feedback Mechanism to Control Vascular Endothelial Growth Factor Receptor-2 Signaling Arterioscler. Thromb. Vasc. Biol., April 1, 2002; 22(4): 617 - 622. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Matsumoto and L. Claesson-Welsh VEGF Receptor Signal Transduction Sci. Signal., December 11, 2001; 2001(112): re21 - re21. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. F. List Vascular Endothelial Growth Factor Signaling Pathway as an Emerging Target in Hematologic Malignancies Oncologist, October 1, 2001; 6(2008): 24 - 31. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Rahimi, V. Dayanir, and K. Lashkari Receptor Chimeras Indicate That the Vascular Endothelial Growth Factor Receptor-1 (VEGFR-1) Modulates Mitogenic Activity of VEGFR-2 in Endothelial Cells J. Biol. Chem., May 26, 2000; 275(22): 16986 - 16992. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Dayanir, R. D. Meyer, K. Lashkari, and N. Rahimi Identification of Tyrosine Residues in Vascular Endothelial Growth Factor Receptor-2/FLK-1 Involved in Activation of Phosphatidylinositol 3-Kinase and Cell Proliferation J. Biol. Chem., May 18, 2001; 276(21): 17686 - 17692. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Zanetti, M. G. Lampugnani, G. Balconi, F. Breviario, M. Corada, L. Lanfrancone, and E. Dejana Vascular Endothelial Growth Factor Induces Shc Association With Vascular Endothelial Cadherin: A Potential Feedback Mechanism to Control Vascular Endothelial Growth Factor Receptor-2 Signaling Arterioscler. Thromb. Vasc. Biol., April 1, 2002; 22(4): 617 - 622. [Abstract] [Full Text] [PDF]
|
|
