TY - JOUR
AU - Alexander, R Wayne
AB - Molecular Medicine Novel Role of ARF6 in Vascular Endothelial Growth Factor–Induced Signaling and Angiogenesis Satoshi Ikeda,* Masuko Ushio-Fukai,* Lian Zuo, Taiki Tojo, Sergey Dikalov, Nikolay A. Patrushev, R. Wayne Alexander Abstract—Vascular endothelial growth factor (VEGF) stimulates endothelial cell (EC) migration and proliferation primarily through the VEGF receptor-2 (VEGFR2). We have shown that VEGF stimulates a Rac1-dependent NAD(P)H oxidase to produce reactive oxygen species (ROS) that are involved in VEGFR2 autophosphorylation and angiogenic- related responses in ECs. The small GTPase ARF6 is involved in membrane trafficking and cell motility; however, its roles in VEGF signaling and physiological responses in ECs are unknown. In this study, we show that overexpression of dominant-negative ARF6 [ARF6(T27N)] almost completely inhibits VEGF-induced Rac1 activation, ROS produc- tion, and VEGFR2 autophosphorylation in ECs. Fractionation of caveolae/lipid raft membranes demonstrates that ARF6, Rac1, and VEGFR2 are localized in caveolin-enriched fractions basally. VEGF stimulation results in the release of VEGFR2 from caveolae/lipid rafts and caveolin-1 without affecting localization of ARF6, Rac1, or caveolin-1 in these fractions. The egress of VEGFR2 from caveolae/lipid rafts is contemporaneous with the tyrosine phosphorylation of caveolin-1 (Tyr14) and VEGFR2 and with their association with each other. ARF6(T27N) significantly inhibits both VEGF-induced responses. Immunofluorescence 
TI - Novel Role of ARF6 in Vascular Endothelial Growth Factor–Induced Signaling and Angiogenesis
JF - Circulation Research
DO - 10.1161/01.RES.0000158286.51045.16
DA - 2005-03-01
UR - https://www.deepdyve.com/lp/wolters-kluwer-health/novel-role-of-arf6-in-vascular-endothelial-growth-factor-ndash-induced-Dhw5qjnIfD
SP - 467
EP - 475
VL - 96
IS - 4
DP - DeepDyve
ER -