TY - JOUR
T1 - VEGF and angiopoietin-1 exert opposing effects on cell junctions by regulating the Rho GEF Syx
AU - Ngok, Siu P.
AU - Geyer, Rory
AU - Liu, Miaoliang
AU - Kourtidis, Antonis
AU - Agrawal, Sudesh
AU - Wu, Chuanshen
AU - Seerapu, Himabindu Reddy
AU - Lewis-Tuffin, Laura J.
AU - Moodie, Karen L.
AU - Huveldt, Deborah
AU - Marx, Ruth
AU - Baraban, Jay M.
AU - Storz, Peter
AU - Horowitz, Arie
AU - Anastasiadis, Panos Z.
PY - 2012/12
Y1 - 2012/12
N2 - Vascular endothelial growth factor (VEGF) and Ang1 (Angiopoietin-1) have opposing effects on vascular permeability, but the molecular basis of these effects is not fully known. We report in this paper that VEGF and Ang1 regulate endothelial cell (EC) junctions by determining the localization of the RhoAspecific guanine nucleotide exchange factor Syx. Syx was recruited to junctions by members of the Crumbs polarity complex and promoted junction integrity by activating Diaphanous. VEGF caused translocation of Syx from cell junctions, promoting junction disassembly, whereas Ang1 maintained Syx at the junctions, inducing junction stabilization. The VEGF-induced translocation of Syx from EC junctions was caused by PKD1 (protein kinase D1)-mediated phosphorylation of Syx at Ser806, which reduced Syx association to its junctional anchors. In support of the pivotal role of Syx in regulating EC junctions, syx-/- mice had defective junctions, resulting in vascular leakiness, edema, and impaired heart function.
AB - Vascular endothelial growth factor (VEGF) and Ang1 (Angiopoietin-1) have opposing effects on vascular permeability, but the molecular basis of these effects is not fully known. We report in this paper that VEGF and Ang1 regulate endothelial cell (EC) junctions by determining the localization of the RhoAspecific guanine nucleotide exchange factor Syx. Syx was recruited to junctions by members of the Crumbs polarity complex and promoted junction integrity by activating Diaphanous. VEGF caused translocation of Syx from cell junctions, promoting junction disassembly, whereas Ang1 maintained Syx at the junctions, inducing junction stabilization. The VEGF-induced translocation of Syx from EC junctions was caused by PKD1 (protein kinase D1)-mediated phosphorylation of Syx at Ser806, which reduced Syx association to its junctional anchors. In support of the pivotal role of Syx in regulating EC junctions, syx-/- mice had defective junctions, resulting in vascular leakiness, edema, and impaired heart function.
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U2 - 10.1083/jcb.201207009
DO - 10.1083/jcb.201207009
M3 - Article
C2 - 23253477
AN - SCOPUS:84871954875
SN - 0021-9525
VL - 199
SP - 1103
EP - 1115
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 7
ER -