scholarly journals PEST Motif Serine and Tyrosine Phosphorylation Controls Vascular Endothelial Growth Factor Receptor 2 Stability and Downregulation

2011 ◽  
Vol 31 (10) ◽  
pp. 2010-2025 ◽  
Author(s):  
R. D. Meyer ◽  
S. Srinivasan ◽  
A. J. Singh ◽  
J. E. Mahoney ◽  
K. R. Gharahassanlou ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Tyrosine Phosphorylation ◽  
Growth Factor Receptor ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

scholarly journals Tyrosine phosphorylation of the vascular endothelial-growth-factor receptor-2 (VEGFR-2) is modulated by Rho proteins

2000 ◽  
Vol 348 (2) ◽  
pp. 273-280 ◽  
Author(s):  
Denis GINGRAS ◽  
Sylvie LAMY ◽  
Richard BÉLIVEAU
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Tyrosine Phosphorylation ◽  
Growth Factor Receptor ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Rho Proteins ◽  
Transient Overexpression ◽  
Endothelial Growth Factor ◽  
Stimulation Of

The effects of Rho-specific modifying toxins on the tyrosine phosphorylation of endothelial cell proteins were investigated. Incubation of the cells with the Rho-activating toxin cytotoxic necrotizing factor 1 (CNF1) induced a marked increase in the tyrosine phosphorylation of a number of signalling intermediates of the vascular endothelial growth factor (VEGF)-mediated cascade, including focal adhesion kinase, paxillin, phospholipase Cγ1 and a Shc-associated protein of 195 kDa. Both CNF1- and VEGF-dependent tyrosine phosphorylation of these proteins were significantly reduced by prior incubation with C3 transferase, a known inhibitor of RhoA function, suggesting a Rho-dependent mechanism. The stimulation of endothelial cells with CNF1 resulted in a marked increase in the tyrosine phosphorylation of the VEGF receptor (VEGFR)-2, which was correlated with a stimulation of its kinase activity and with its association with downstream tyrosine phosphorylated proteins. The stimulatory effect of CNF1 was specific for VEGFR-2 since the phosphotyrosine content of VEGFR-1 was not affected by the toxin. Transient overexpression of a dominant-active RhoA mutant also induced an increase in the tyrosine phosphorylation of the VEGFR-2, whereas overexpression of a dominant-inactive form of the protein was without effect. Taken together, these results indicate that Rho proteins may play an important role in angiogenesis by modulating the tyrosine phosphorylation levels of VEGFR-2.

scholarly journals A Role for Cadherin-5 in Regulation of Vascular Endothelial Growth Factor Receptor 2 Activity in Endothelial Cells

1999 ◽  
Vol 10 (10) ◽  
pp. 3401-3407 ◽  
Author(s):  
Nader Rahimi ◽  
Andrius Kazlauskas
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cells ◽  
Growth Factor ◽  
Tyrosine Phosphorylation ◽  
Cell Density ◽  
Critical Role ◽  
Growth Factor Receptor ◽  
Cell Contact ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

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 α 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.

Fortgeschrittenes medulläres Schilddrüsenkarzinom: Vandetanib verbessert das progressionsfreie Überleben

2012 ◽  
Vol 03 (02) ◽  
pp. 93-92
Author(s):  
Alexander Kretzschmar
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Phase Iii ◽  
Vascular Endothelial ◽  
Medulläres Schilddrüsenkarzinom ◽  
Epidermal Growth ◽  
Endothelial Growth Factor

Vandetanib ist ein oraler Hemmer des RET-Kinase-, VEGF (Vascular Endothelial Growth Factor Receptor)- und EGFR (Epidermal Growth Factor Receptor)-Signalwegs. In einer zulassungsrelevanten, randomisierten, doppelblinden, placebokontrollierten Phase- III-Studie verlängerte der Tyrosinkinasehemmer das progressionsfreie Überleben (PFS) signifikant länger als Placebo.

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