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Structural Basis for Vascular Endothelial Growth Factor Receptor Activation and Implications for Disease Therapy

Shaik, F; Cuthbert, GA; Homer-Vanniasinkam, S; Muench, SP; Ponnambalam, S; Harrison, MA; (2020) Structural Basis for Vascular Endothelial Growth Factor Receptor Activation and Implications for Disease Therapy. Biomolecules , 10 (12) 10.3390/biom10121673. Green open access

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Abstract

Vascular endothelial growth factors (VEGFs) bind to membrane receptors on a wide variety of cells to regulate diverse biological responses. The VEGF-A family member promotes vasculogenesis and angiogenesis, processes which are essential for vascular development and physiology. As angiogenesis can be subverted in many disease states, including tumour development and progression, there is much interest in understanding the mechanistic basis for how VEGF-A regulates cell and tissue function. VEGF-A binds with high affinity to two VEGF receptor tyrosine kinases (VEGFR1, VEGFR2) and with lower affinity to co-receptors called neuropilin-1 and neuropilin-2 (NRP1, NRP2). Here, we use a structural viewpoint to summarise our current knowledge of VEGF-VEGFR activation and signal transduction. As targeting VEGF-VEGFR activation holds much therapeutic promise, we examine the structural basis for anti-angiogenic therapy using small-molecule compounds such as tyrosine kinase inhibitors that block VEGFR activation and downstream signalling. This review provides a rational basis towards reconciling VEGF and VEGFR structure and function in developing new therapeutics for a diverse range of ailments.

Type: Article
Title: Structural Basis for Vascular Endothelial Growth Factor Receptor Activation and Implications for Disease Therapy
Location: Switzerland
Open access status: An open access version is available from UCL Discovery
DOI: 10.3390/biom10121673
Publisher version: http://dx.doi.org/10.3390/biom10121673
Language: English
Additional information: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
Keywords: VEGFR, aflibercept, angiogenesis, bevacizumab, cancer, receptor tyrosine kinase, signal transduction, sunitinib
UCL classification: UCL
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Mechanical Engineering
URI: https://discovery.ucl.ac.uk/id/eprint/10118116
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