Vascular Endothelial Growth Factor (VEGF) Promotes Assembly of the p130Cas Interactome to Drive Endothelial Chemotactic Signaling and Angiogenesis.
Loading...
Embargo End Date
ICR Authors
Authors
Evans, IM
Kennedy, SA
Paliashvili, K
Santra, T
Yamaji, M
Lovering, RC
Britton, G
Frankel, P
Kolch, W
Zachary, IC
Kennedy, SA
Paliashvili, K
Santra, T
Yamaji, M
Lovering, RC
Britton, G
Frankel, P
Kolch, W
Zachary, IC
Document Type
Journal Article
Date
2017-02-01
Date Accepted
2016-12-15
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.
Citation
Molecular & cellular proteomics : MCP, 2017, 16 (2), pp. 168 - 180
Source Title
Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
ISSN
1535-9476
eISSN
1535-9484
Collections
Research Team
Cancer Stem Cell