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

Cell. 1999 Oct 29;99(3):301-12. doi: 10.1016/s0092-8674(00)81661-x.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, CD
  • Cadherins / analysis
  • Cadherins / physiology*
  • Calcium / metabolism
  • Cell Adhesion / drug effects
  • Cell Adhesion / physiology*
  • Cells, Cultured
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / physiology*
  • Female
  • Humans
  • I-kappa B Proteins*
  • Immediate-Early Proteins / genetics
  • Immediate-Early Proteins / physiology
  • Intercellular Junctions / drug effects
  • Intercellular Junctions / physiology*
  • Lysophospholipids*
  • Mice
  • Mice, Nude
  • Models, Biological
  • Morphogenesis / drug effects
  • NF-KappaB Inhibitor alpha
  • Neovascularization, Physiologic / drug effects
  • Neovascularization, Physiologic / physiology*
  • Oocytes / physiology
  • Receptors, Cell Surface / physiology
  • Receptors, G-Protein-Coupled*
  • Receptors, Lysophospholipid
  • Recombinant Proteins / metabolism
  • Sphingosine / analogs & derivatives*
  • Sphingosine / pharmacology
  • Umbilical Veins
  • Xenopus laevis

Substances

  • Antigens, CD
  • Cadherins
  • DNA-Binding Proteins
  • I-kappa B Proteins
  • Immediate-Early Proteins
  • Lysophospholipids
  • NFKBIA protein, human
  • Nfkbia protein, mouse
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled
  • Receptors, Lysophospholipid
  • Recombinant Proteins
  • cadherin 5
  • NF-KappaB Inhibitor alpha
  • sphingosine 1-phosphate
  • Sphingosine
  • Calcium