Vascular Endothelial Growth Factor (VEGF) Promotes Assembly of the p130Cas Interactome to Drive Endothelial Chemotactic Signaling and Angiogenesis.
View/ Open
Date
2017-02-01ICR Author
Author
Evans, IM
Kennedy, SA
Paliashvili, K
Santra, T
Yamaji, M
Lovering, RC
Britton, G
Frankel, P
Kolch, W
Zachary, IC
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Humans
Vascular Endothelial Growth Factor A
Proteomics
Signal Transduction
Chemotaxis
Neovascularization, Physiologic
Databases, Protein
Crk-Associated Substrate Protein
Mass Spectrometry
Human Umbilical Vein Endothelial Cells
Protein Interaction Maps
Research team
Cancer Stem Cell
Language
eng
Date accepted
2016-12-15
License start date
2017-02
Citation
Molecular & cellular proteomics : MCP, 2017, 16 (2), pp. 168 - 180
Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC