title: Vascular Endothelial Growth Factor (VEGF) Promotes Assembly of the p130Cas Interactome to Drive Endothelial Chemotactic Signaling and Angiogenesis.
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 signaling, endothelial polarization, 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.
authors.affiliation: From the ‡Centre for Cardiovascular Biology and Medicine, Division of Medicine The Rayne Building, University College London, London WC1E 6JJ, United Kingdom.
authors.forename: Ian M
authors.initials: IM
authors.lastname: Evans
authors.affiliation: §Systems Biology Ireland, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Susan A
authors.initials: SA
authors.lastname: Kennedy
authors.affiliation: From the ‡Centre for Cardiovascular Biology and Medicine, Division of Medicine The Rayne Building, University College London, London WC1E 6JJ, United Kingdom.
authors.forename: Ketevan
authors.initials: K
authors.lastname: Paliashvili
authors.affiliation: §Systems Biology Ireland, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Tapesh
authors.initials: T
authors.lastname: Santra
authors.affiliation: From the ‡Centre for Cardiovascular Biology and Medicine, Division of Medicine The Rayne Building, University College London, London WC1E 6JJ, United Kingdom.
authors.forename: Maiko
authors.initials: M
authors.lastname: Yamaji
authors.affiliation: **Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, The Rayne Building, University College London, London WC1E 6JJ, United Kingdom.
authors.forename: Ruth C
authors.initials: RC
authors.lastname: Lovering
authors.affiliation: From the ‡Centre for Cardiovascular Biology and Medicine, Division of Medicine The Rayne Building, University College London, London WC1E 6JJ, United Kingdom.
authors.forename: Gary
authors.initials: G
authors.lastname: Britton
authors.affiliation: From the ‡Centre for Cardiovascular Biology and Medicine, Division of Medicine The Rayne Building, University College London, London WC1E 6JJ, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Frankel
authors.affiliation: §Systems Biology Ireland, University College Dublin, Belfield, Dublin 4, Ireland.|¶Conway Institute of Biomolecular & Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.|‖School of Medicine and Medical Science, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Walter
authors.initials: W
authors.lastname: Kolch
authors.affiliation: From the ‡Centre for Cardiovascular Biology and Medicine, Division of Medicine The Rayne Building, University College London, London WC1E 6JJ, United Kingdom; I.Zachary@ucl.ac.uk.
authors.forename: Ian C
authors.initials: IC
authors.lastname: Zachary
mesh_terms: D002633:Chemotaxis / Q000187:drug effects*; D050719:Crk-Associated Substrate Protein / Q000378:metabolism*; D030562:Databases, Protein; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D013058:Mass Spectrometry; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D060066:Protein Interaction Maps / Q000187:drug effects; D040901:Proteomics / Q000379:methods*; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
chemical_list: C493841:BCAR1 protein, human; D050719:Crk-Associated Substrate Protein; D042461:Vascular Endothelial Growth Factor A