%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 }