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VEGF promotes assembly of the p130Cas interactome to drive endothelial chemotactic signalling and angiogenesis

Evans, IM; Kennedy, SA; Paliashvili, K; Santra, T; Yamaji, M; Lovering, RC; Britton, G; ... Zachary, IC; + view all (2017) VEGF promotes assembly of the p130Cas interactome to drive endothelial chemotactic signalling and angiogenesis. Molecular and Cellular Proteomics , 16 pp. 168-180. 10.1074/mcp.M116.064428. Green open access

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Abstract

p130Cas is a polyvalent adapter protein essential for cardiovascular development, and with a key role in cell movement. In order to identify the pathways by which p130Cas exerts its biological functions in endothelial cells we mapped the p130Cas interactome and its dynamic changes in response to VEGF using high-resolution mass spectrometry and reconstruction of protein interaction (PPI) networks with the aid of multiple PPI databases. VEGF enriched the p130Cas interactome in proteins involved in actin cytoskeletal dynamics and cell movement, including actin-binding proteins, small GTPases and regulators or binders of GTPases. Detailed studies showed that p130Cas association of the GTPase-binding scaffold protein, IQGAP1, plays a key role in VEGF chemotactic signalling, endothelial polarisation, VEGF-induced cell migration, and endothelial tube formation. These findings indicate a cardinal role for assembly of the p130Cas interactome in mediating the cell migratory response to VEGF in angiogenesis, and provide a basis for further studies of p130Cas in cell movement.

Type: Article
Title: VEGF promotes assembly of the p130Cas interactome to drive endothelial chemotactic signalling and angiogenesis
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1074/mcp.M116.064428
Publisher version: http://dx.doi.org/10.1074/mcp.M116.064428
Language: English
Additional information: This research was originally published in Evans, IM; Kennedy, SA; Paliashvili, K; Santra, T; Yamaji, M; Lovering, RC; Britton, G; (2016) VEGF promotes assembly of the p130Cas interactome to drive endothelial chemotactic signalling and angiogenesis. Molecular and Cellular Proteomics 10.1074/mcp.M116.064428. © the American Society for Biochemistry and Molecular Biology. Final version free via Creative Commons CC-BY license.
Keywords: Cardiovascular function or biology, Label-free quantification, Mass Spectrometry, Protein-Protein Interactions*, Signal Transduction*
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Experimental and Translational Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Pre-clinical and Fundamental Science
URI: https://discovery.ucl.ac.uk/id/eprint/1534369
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