Vascular endothelial cell adherens junction assembly and morphogenesis induced by sphingosine-1-phosphate

被引:886
作者
Lee, MJ [1 ]
Thangada, S [1 ]
Claffey, KP [1 ]
Ancellin, N [1 ]
Liu, CH [1 ]
Kluk, M [1 ]
Volpi, M [1 ]
Sha'afi, RI [1 ]
Hla, T [1 ]
机构
[1] Univ Connecticut, Ctr Hlth, Dept Physiol, Ctr Vasc Biol, Farmington, CT 06030 USA
关键词
D O I
10.1016/S0092-8674(00)81661-X
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Vascular endothelial cells undergo morphogenesis into capillary networks in response to angiogenic factors. We show here that sphingosine-1-phosphate (SPP), a platelet-derived bioactive lipid, activates the EDG-1 and -3 subtypes of G protein-coupled receptors on endothelial cells to regulate angiogenesis. SPP induces the G(i)/mitogen-activated protein kinase/cell survival pathway and the smalt GTPase Rho- and Rac-coupled adherens junction assembly. Both EDG-1- and EDG-3-regulated signaling pathways are required for endothelial cell morphogenesis into capillary-like networks. Indeed, SPP synergized with polypeptide angiogenic growth factors in the formation of mature neovessels in vivo. These data define SPP as a novel regulator of angiogenesis.
引用
收藏
页码:301 / 312
页数:12
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