Protein Tyrosine Kinase Inhibitors Act Downstream of IL-1α and LPS Stimulated MAP-Kinase Phosphorylation to Inhibit Expression of E-Selectin on Human Umbilical Vein Endothelial Cells

1996 ◽  
Vol 3 (6) ◽  
pp. 511-525 ◽  
Author(s):  
Peter Adamson ◽  
Miranda Tighe ◽  
Jeremy D. Pearson
Keyword(s):  
Endothelial Cells ◽  
Tyrosine Kinase ◽  
Map Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Protein Tyrosine Kinase ◽  
Kinase Inhibitors ◽  
Umbilical Vein ◽  
Human Umbilical Vein ◽  
Umbilical Vein Endothelial Cells ◽  
Kinase Phosphorylation

scholarly journals KDR activation is crucial for VEGF165-mediated Ca2+mobilization in human umbilical vein endothelial cells

1999 ◽  
Vol 276 (1) ◽  
pp. C176-C181 ◽  
Author(s):  
Sonia A. Cunningham ◽  
Tuan M. Tran ◽  
M. Pia Arrate ◽  
Robert Bjercke ◽  
Tommy A. Brock
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Tyrosine Kinase ◽  
Umbilical Vein ◽  
Vascular Endothelial Cell ◽  
Vascular Endothelial ◽  
Human Umbilical Vein ◽  
Intracellular Ca ◽  
Umbilical Vein Endothelial Cells

We have prepared a polyclonal mouse antibody directed against the first three immunoglobulin-like domains of the kinase insert domain-containing receptor (KDR) tyrosine kinase. It possesses the ability to inhibit binding of the 165-amino acid splice variant of vascular endothelial cell growth factor (VEGF165) to recombinant KDR in vitro as well as to reduce VEGF165binding to human umbilical vein endothelial cells (HUVEC). These results confirm that the first three immunoglobulin-like domains of KDR are involved in VEGF165interactions. The anti-KDR antibody is able to completely block VEGF165-mediated intracellular Ca2+mobilization in HUVEC. Therefore, it appears that binding of VEGF165to the fms-like tyrosine kinase (Flt-1) in these cells does not translate into a Ca2+response. This is further exemplified by the lack of response to placental growth factor (PlGF), an Flt-1-specific ligand. Additionally, PlGF is unable to potentiate the effects of submaximal concentrations of VEGF165. Surprisingly, the VEGF-PlGF heterodimer was also very inefficient at eliciting a Ca2+signaling event in HUVEC. We conclude that KDR activation is crucial for mobilization of intracellular Ca2+in HUVEC in response to VEGF165.

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