Vascular endothelial cell adherens junction assembly and morphogenesis induced by sphingosine-1-phosphate. |
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| Authors: | M J Lee S Thangada K P Claffey N Ancellin C H Liu M Kluk M Volpi R I Sha'afi T Hla |
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| Institution: | Center for Vascular Biology, Department of Physiology, University of Connecticut Health Center, Farmington 06030-3501, USA. |
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| Abstract: | 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 Gi/mitogen-activated protein kinase/cell survival pathway and the small GTPase Rho- and Raccoupled 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. |
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