Structural Basis for Vascular Endothelial Growth Factor Receptor Activation and Implications for Disease Therapy
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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-12-01
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| Series: | Biomolecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-273X/10/12/1673 |
| _version_ | 1827700047027896320 |
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| author | Faheem Shaik Gary A. Cuthbert Shervanthi Homer-Vanniasinkam Stephen P. Muench Sreenivasan Ponnambalam Michael A. Harrison |
| author_facet | Faheem Shaik Gary A. Cuthbert Shervanthi Homer-Vanniasinkam Stephen P. Muench Sreenivasan Ponnambalam Michael A. Harrison |
| author_sort | Faheem Shaik |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T14:03:57Z |
| format | Article |
| id | doaj.art-759e775db3f140f49d16cbafb710154f |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T14:03:57Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-759e775db3f140f49d16cbafb710154f2023-11-21T00:50:58ZengMDPI AGBiomolecules2218-273X2020-12-011012167310.3390/biom10121673Structural Basis for Vascular Endothelial Growth Factor Receptor Activation and Implications for Disease TherapyFaheem Shaik0Gary A. Cuthbert1Shervanthi Homer-Vanniasinkam2Stephen P. Muench3Sreenivasan Ponnambalam4Michael A. Harrison5School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, UKFaculty of Medicine and Health, University of Leeds, Leeds LS2 9JT, UKFaculty of Medicine and Health, University of Leeds, Leeds LS2 9JT, UKSchool of Biomedical Sciences, University of Leeds, Leeds LS2 9JT, UKSchool of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, UKFaculty of Medicine and Health, University of Leeds, Leeds LS2 9JT, UKVascular 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.https://www.mdpi.com/2218-273X/10/12/1673angiogenesisVEGFRreceptor tyrosine kinasesignal transductioncancerbevacizumab |
| spellingShingle | Faheem Shaik Gary A. Cuthbert Shervanthi Homer-Vanniasinkam Stephen P. Muench Sreenivasan Ponnambalam Michael A. Harrison Structural Basis for Vascular Endothelial Growth Factor Receptor Activation and Implications for Disease Therapy Biomolecules angiogenesis VEGFR receptor tyrosine kinase signal transduction cancer bevacizumab |
| title | Structural Basis for Vascular Endothelial Growth Factor Receptor Activation and Implications for Disease Therapy |
| title_full | Structural Basis for Vascular Endothelial Growth Factor Receptor Activation and Implications for Disease Therapy |
| title_fullStr | Structural Basis for Vascular Endothelial Growth Factor Receptor Activation and Implications for Disease Therapy |
| title_full_unstemmed | Structural Basis for Vascular Endothelial Growth Factor Receptor Activation and Implications for Disease Therapy |
| title_short | Structural Basis for Vascular Endothelial Growth Factor Receptor Activation and Implications for Disease Therapy |
| title_sort | structural basis for vascular endothelial growth factor receptor activation and implications for disease therapy |
| topic | angiogenesis VEGFR receptor tyrosine kinase signal transduction cancer bevacizumab |
| url | https://www.mdpi.com/2218-273X/10/12/1673 |
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