Swendeman, Steven; Mendelson, Karen; Weskamp, Gisela; Horiuchi, Keisuke; Deutsch, Urban; Scherle, Peggy; Hooper, Andrea; Rafii, Shahin; Blobel, Carl P (2008). VEGF-A stimulates ADAM17-dependent shedding of VEGFR2 and crosstalk between VEGFR2 and ERK signaling. Circulation research, 103(9), pp. 916-8. Baltimore, Md.: Lippincott Williams & Wilkins 10.1161/CIRCRESAHA.108.184416
Full text not available from this repository. (Request a copy)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, providing evidence for an ADAM17-dependent crosstalk between the VEGFR2 and ERK signaling. Targeting the sheddases of VEGFR2 or NRP-1 might offer new opportunities to modulate VEGF-A signaling, an already-established target for treatment of pathological neovascularization.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute |
UniBE Contributor: |
Deutsch, Urban |
ISSN: |
0009-7330 |
ISBN: |
18818406 |
Publisher: |
Lippincott Williams & Wilkins |
Language: |
English |
Submitter: |
Factscience Import |
Date Deposited: |
04 Oct 2013 15:05 |
Last Modified: |
05 Dec 2022 14:20 |
Publisher DOI: |
10.1161/CIRCRESAHA.108.184416 |
PubMed ID: |
18818406 |
Web of Science ID: |
000260308500006 |
URI: |
https://boris.unibe.ch/id/eprint/28201 (FactScience: 118528) |
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