RGD Reference Report - IQGAP1, a novel vascular endothelial growth factor receptor binding protein, is involved in reactive oxygen species--dependent endothelial migration and proliferation. - Rat Genome Database

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IQGAP1, a novel vascular endothelial growth factor receptor binding protein, is involved in reactive oxygen species--dependent endothelial migration and proliferation.

Authors: Yamaoka-Tojo, M  Ushio-Fukai, M  Hilenski, L  Dikalov, SI  Chen, YE  Tojo, T  Fukai, T  Fujimoto, M  Patrushev, NA  Wang, N  Kontos, CD  Bloom, GS  Alexander, RW 
Citation: Yamaoka-Tojo M, etal., Circ Res. 2004 Aug 6;95(3):276-83. Epub 2004 Jun 24.
RGD ID: 11049588
Pubmed: PMID:15217908   (View Abstract at PubMed)
DOI: DOI:10.1161/01.RES.0000136522.58649.60   (Journal Full-text)

Endothelial cell (EC) proliferation and migration are important for reendothelialization and angiogenesis. We have demonstrated that reactive oxygen species (ROS) derived from the small GTPase Rac1-dependent NAD(P)H oxidase are involved in vascular endothelial growth factor (VEGF)-mediated endothelial responses mainly through the VEGF type2 receptor (VEGFR2). Little is known about the underlying molecular mechanisms. IQGAP1 is a scaffolding protein that controls cellular motility and morphogenesis by interacting directly with cytoskeletal, cell adhesion, and small G proteins, including Rac1. In this study, we show that IQGAP1 is robustly expressed in ECs and binds to the VEGFR2. A pulldown assay using purified proteins demonstrates that IQGAP1 directly interacts with active VEGFR2. In cultured ECs, VEGF stimulation rapidly promotes recruitment of Rac1 to IQGAP1, which inducibly binds to VEGFR2 and which, in turn, is associated with tyrosine phosphorylation of IQGAP1. Endogenous IQGAP1 knockdown by siRNA shows that IQGAP1 is involved in VEGF-stimulated ROS production, Akt phosphorylation, endothelial migration, and proliferation. Wound assays reveal that IQGAP1 and phosphorylated VEGFR2 accumulate and colocalize at the leading edge in actively migrating ECs. Moreover, we found that IQGAP1 expression is dramatically increased in the VEGFR2-positive regenerating EC layer in balloon-injured rat carotid artery. These results suggest that IQGAP1 functions as a VEGFR2-associated scaffold protein to organize ROS-dependent VEGF signaling, thereby promoting EC migration and proliferation, which may contribute to repair and maintenance of the functional integrity of established blood vessels.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
IQGAP1HumanVascular System Injuries  ISOIqgap1 (Rattus norvegicus) RGD 
Iqgap1RatVascular System Injuries  IEP  RGD 
Iqgap1MouseVascular System Injuries  ISOIqgap1 (Rattus norvegicus) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Iqgap1  (IQ motif containing GTPase activating protein 1)

Genes (Mus musculus)
Iqgap1  (IQ motif containing GTPase activating protein 1)

Genes (Homo sapiens)
IQGAP1  (IQ motif containing GTPase activating protein 1)


Additional Information