Vascular endothelial cell adherens junction assembly and morphogenesis induced by sphingosine-1-phosphate.
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.
Lee
M J
MJ
Center for Vascular Biology, Department of Physiology, University of Connecticut Health Center, Farmington 06030-3501, USA.
Thangada
S
S
Claffey
K P
KP
Ancellin
N
N
Liu
C H
CH
Kluk
M
M
Volpi
M
M
Sha'afi
R I
RI
Hla
T
T
D000818:Animals; D015703:Antigens, CD; D015820:Cadherins / Q000032:analysis / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006801:Humans; D020672:I-kappa B Proteins; D017874:Immediate-Early Proteins / Q000235:genetics / Q000502:physiology; D007365:Intercellular Junctions / Q000187:drug effects / Q000502:physiology*; D008246:Lysophospholipids; D051379:Mice; D008819:Mice, Nude; D008954:Models, Biological; D009024:Morphogenesis / Q000187:drug effects; D000072000:NF-KappaB Inhibitor alpha; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D009865:Oocytes / Q000502:physiology; D011956:Receptors, Cell Surface / Q000502:physiology; D043562:Receptors, G-Protein-Coupled; D049312:Receptors, Lysophospholipid; D011994:Recombinant Proteins / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014471:Umbilical Veins; D014982:Xenopus laevis; D000099152:Cadherin 5
D015703:Antigens, CD; D015820:Cadherins; D002118:Calcium; D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D017874:Immediate-Early Proteins; D008246:Lysophospholipids; D000072000:NF-KappaB Inhibitor alpha; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D049312:Receptors, Lysophospholipid; D011994:Recombinant Proteins; D013110:Sphingosine; D000099152:Cadherin 5; C000606204:NFKBIA protein, human; C000606205:Nfkbia protein, mouse; C060506:sphingosine 1-phosphate