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

TitleVascular endothelial cell adherens junction assembly and morphogenesis induced by sphingosine-1-phosphate.
Publication TypeJournal Article
Year of Publication1999
AuthorsLee MJ, Thangada S, Claffey KP, Ancellin N, Liu CH, Kluk M, Volpi M, Sha'afi RI, Hla T
Date Published1999 Oct 29
KeywordsAnimals, Antigens, CD, Cadherins, Calcium, Cell Adhesion, Cells, Cultured, DNA-Binding Proteins, Endothelium, Vascular, Female, Humans, I-kappa B Proteins, Immediate-Early Proteins, Intercellular Junctions, Lysophospholipids, Mice, Mice, Nude, Models, Biological, Morphogenesis, Neovascularization, Physiologic, NF-KappaB Inhibitor alpha, Oocytes, Receptors, Cell Surface, Receptors, G-Protein-Coupled, Receptors, Lysophospholipid, Recombinant Proteins, Sphingosine, Umbilical Veins, Xenopus laevis

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.

Alternate JournalCell
PubMed ID10555146
Grant ListCA64436 / CA / NCI NIH HHS / United States
DK45659 / DK / NIDDK NIH HHS / United States
HL54710 / HL / NHLBI NIH HHS / United States
Related Faculty: 
Michael Kluk, M.D., Ph.D.

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