Vascular endothelial growth factor (VEGF)-A and the VEGF receptors are critical for regulating angiogenesis during development and homeostasis and in pathological conditions, such as cancer and proliferative retinopathies. Most effects of VEGF-A are mediated by the VEGFR2 and its coreceptor, neuropilin (NRP)-1. Here, we show that VEGFR2 is shed from cells by the metalloprotease disintegrin ADAM17, whereas NRP-1 is released by ADAM10. VEGF-A enhances VEGFR2 shedding by ADAM17 but not shedding of NRP-1 by ADAM10. VEGF-A activates ADAM17 via the extracellular signal-regulated kinase (ERK) and mitogen-activated protein kinase pathways, thereby also triggering shedding of other ADAM17 substrates, including tumor necrosis factor alpha, transforming growth factor alpha, heparin-binding epidermal growth factor-like growth factor, and Tie-2. Interestingly, an ADAM17-selective inhibitor shortens the duration of VEGF-A-stimulated ERK phosphorylation in human umbilical vein endothelial cells, prov
%0 Journal Article
%1 Swendeman.2008
%A Swendeman, S.
%A Mendelson, K.
%A Weskamp, G.
%A Horiuchi, K.
%A Deutsch, U.
%A Scherle, P.
%A Hooper, A.
%A Rafii, S.
%A Blobel, C. P.
%D 2008
%J Circ.Res.
%K A ADAM Amyloid Animals Cells Cercopithecus Cos Endothelial Extracellular Factor Factor-alpha Factors Fibroblasts Fusion Growth Human Humans Kinases Knockout MAP Membrane Mice Necrosis Neuropilin-1 Phosphorylation Precursor Protein Proteins Receptor-2 Recombinant Research Secretases Signal Signal-Regulated Swine Time Transduction Transfection Tumor Vascular aethiops cells deficiency enzymology genetics metabolism protein surgery
%N 9
%P 916-918
%T VEGF-A stimulates ADAM17-dependent shedding of VEGFR2 and crosstalk between VEGFR2 and ERK signaling
%U PM:18818406
%V 103
%X Vascular endothelial growth factor (VEGF)-A and the VEGF receptors are critical for regulating angiogenesis during development and homeostasis and in pathological conditions, such as cancer and proliferative retinopathies. Most effects of VEGF-A are mediated by the VEGFR2 and its coreceptor, neuropilin (NRP)-1. Here, we show that VEGFR2 is shed from cells by the metalloprotease disintegrin ADAM17, whereas NRP-1 is released by ADAM10. VEGF-A enhances VEGFR2 shedding by ADAM17 but not shedding of NRP-1 by ADAM10. VEGF-A activates ADAM17 via the extracellular signal-regulated kinase (ERK) and mitogen-activated protein kinase pathways, thereby also triggering shedding of other ADAM17 substrates, including tumor necrosis factor alpha, transforming growth factor alpha, heparin-binding epidermal growth factor-like growth factor, and Tie-2. Interestingly, an ADAM17-selective inhibitor shortens the duration of VEGF-A-stimulated ERK phosphorylation in human umbilical vein endothelial cells, prov
@article{Swendeman.2008,
abstract = {Vascular endothelial growth factor (VEGF)-A and the VEGF receptors are critical for regulating angiogenesis during development and homeostasis and in pathological conditions, such as cancer and proliferative retinopathies. Most effects of VEGF-A are mediated by the VEGFR2 and its coreceptor, neuropilin (NRP)-1. Here, we show that VEGFR2 is shed from cells by the metalloprotease disintegrin ADAM17, whereas NRP-1 is released by ADAM10. VEGF-A enhances VEGFR2 shedding by ADAM17 but not shedding of NRP-1 by ADAM10. VEGF-A activates ADAM17 via the extracellular signal-regulated kinase (ERK) and mitogen-activated protein kinase pathways, thereby also triggering shedding of other ADAM17 substrates, including tumor necrosis factor alpha, transforming growth factor alpha, heparin-binding epidermal growth factor-like growth factor, and Tie-2. Interestingly, an ADAM17-selective inhibitor shortens the duration of VEGF-A-stimulated ERK phosphorylation in human umbilical vein endothelial cells, prov},
added-at = {2010-02-05T11:28:39.000+0100},
author = {Swendeman, S. and Mendelson, K. and Weskamp, G. and Horiuchi, K. and Deutsch, U. and Scherle, P. and Hooper, A. and Rafii, S. and Blobel, C. P.},
biburl = {https://www.bibsonomy.org/bibtex/243e4c02a29bd57d4267106b87d1e3b33/kanefendt},
interhash = {bc8f920d5335e2898ac95ef0db230019},
intrahash = {43e4c02a29bd57d4267106b87d1e3b33},
journal = {Circ.Res.},
keywords = {A ADAM Amyloid Animals Cells Cercopithecus Cos Endothelial Extracellular Factor Factor-alpha Factors Fibroblasts Fusion Growth Human Humans Kinases Knockout MAP Membrane Mice Necrosis Neuropilin-1 Phosphorylation Precursor Protein Proteins Receptor-2 Recombinant Research Secretases Signal Signal-Regulated Swine Time Transduction Transfection Tumor Vascular aethiops cells deficiency enzymology genetics metabolism protein surgery},
number = 9,
pages = {916-918},
timestamp = {2010-02-05T11:28:50.000+0100},
title = {VEGF-A stimulates ADAM17-dependent shedding of VEGFR2 and crosstalk between VEGFR2 and ERK signaling},
url = {PM:18818406},
volume = 103,
year = 2008
}