Vascular endothelial growth factor receptor-1/fms-related tyrosine kinase 1 (VEGFR-1/FLT1) is expressed as a membrane-bound receptor tyrosine kinase and as an alternatively spliced soluble protein (sVEGFR-1) containing the 1-6 IgG-like domain of its ectodomain. sVEGFR-1 is known as a naturally occurring inhibitor of angiogenesis and as a surrogate marker for cancer progression; it is also linked to pregnancy-induced hypertension called preeclampsia and to avascularity of normal cornea. It remains an open question whether alternative mRNA splicing is the only mechanism by which sVEGFR-1 is generated. In this study, we show that in leukemic cancer cells, PlGF and VEGF-A both induce tyrosine phosphorylation of VEGFR-1 and render it susceptible to ectodomain shedding, resulting in the generation of sVEGFR-1 and an intracellular cytoplasmic fragment. Activation of protein kinase C and tumor necrosis factor-alpha-converting enzyme family metalloproteases are critically required for the occur
%0 Journal Article
%1 Rahimi.2009
%A Rahimi, N.
%A Golde, T. E.
%A Meyer, R. D.
%D 2009
%J Cancer Res.
%K Amyloid B-Cell C Cell Cells Cytoplasm Diffuse Endothelial Factor Growth Humans Hypertension Kinase Large Ligands Lymphoma Membrane Necrosis Phosphorylation Precursor Protein Receptor-1 Research Secretases Signal Structure Tertiary Transduction Tyrosine Vascular biosynthesis cells enzymology metabolism pathology protein
%N 6
%P 2607-2614
%T Identification of ligand-induced proteolytic cleavage and ectodomain shedding of VEGFR-1/FLT1 in leukemic cancer cells
%U PM:19276374
%V 69
%X Vascular endothelial growth factor receptor-1/fms-related tyrosine kinase 1 (VEGFR-1/FLT1) is expressed as a membrane-bound receptor tyrosine kinase and as an alternatively spliced soluble protein (sVEGFR-1) containing the 1-6 IgG-like domain of its ectodomain. sVEGFR-1 is known as a naturally occurring inhibitor of angiogenesis and as a surrogate marker for cancer progression; it is also linked to pregnancy-induced hypertension called preeclampsia and to avascularity of normal cornea. It remains an open question whether alternative mRNA splicing is the only mechanism by which sVEGFR-1 is generated. In this study, we show that in leukemic cancer cells, PlGF and VEGF-A both induce tyrosine phosphorylation of VEGFR-1 and render it susceptible to ectodomain shedding, resulting in the generation of sVEGFR-1 and an intracellular cytoplasmic fragment. Activation of protein kinase C and tumor necrosis factor-alpha-converting enzyme family metalloproteases are critically required for the occur
@article{Rahimi.2009,
abstract = {Vascular endothelial growth factor receptor-1/fms-related tyrosine kinase 1 (VEGFR-1/FLT1) is expressed as a membrane-bound receptor tyrosine kinase and as an alternatively spliced soluble protein (sVEGFR-1) containing the 1-6 IgG-like domain of its ectodomain. sVEGFR-1 is known as a naturally occurring inhibitor of angiogenesis and as a surrogate marker for cancer progression; it is also linked to pregnancy-induced hypertension called preeclampsia and to avascularity of normal cornea. It remains an open question whether alternative mRNA splicing is the only mechanism by which sVEGFR-1 is generated. In this study, we show that in leukemic cancer cells, PlGF and VEGF-A both induce tyrosine phosphorylation of VEGFR-1 and render it susceptible to ectodomain shedding, resulting in the generation of sVEGFR-1 and an intracellular cytoplasmic fragment. Activation of protein kinase C and tumor necrosis factor-alpha-converting enzyme family metalloproteases are critically required for the occur},
added-at = {2010-02-05T11:28:39.000+0100},
author = {Rahimi, N. and Golde, T. E. and Meyer, R. D.},
biburl = {https://www.bibsonomy.org/bibtex/25a47ea780da22e7f86a3cef06ec574cb/kanefendt},
interhash = {ab0820afabce041f8530b6a3fe32bab7},
intrahash = {5a47ea780da22e7f86a3cef06ec574cb},
journal = {Cancer Res.},
keywords = {Amyloid B-Cell C Cell Cells Cytoplasm Diffuse Endothelial Factor Growth Humans Hypertension Kinase Large Ligands Lymphoma Membrane Necrosis Phosphorylation Precursor Protein Receptor-1 Research Secretases Signal Structure Tertiary Transduction Tyrosine Vascular biosynthesis cells enzymology metabolism pathology protein},
number = 6,
pages = {2607-2614},
timestamp = {2010-02-05T11:28:53.000+0100},
title = {Identification of ligand-induced proteolytic cleavage and ectodomain shedding of VEGFR-1/FLT1 in leukemic cancer cells},
url = {PM:19276374},
volume = 69,
year = 2009
}