Sphingosine-1-phosphate signaling via the EDG-1 family of G-protein-coupled receptors Review uri icon

Overview

MeSH Major

  • GTP-Binding Proteins
  • Immediate-Early Proteins
  • Lysophospholipids
  • Receptors, G-Protein-Coupled
  • Signal Transduction
  • Sphingosine

abstract

  • The bioactive lipid sphingosine-1-phosphate (SPP) is abundantly formed and released during the activation of platelets by thrombotic stimuli. Once exported, SPP interacts with the G-protein-coupled receptors (GPCR) of the EDG-1 family. SPP binds to EDG-1 with the dissociation constant of approximately 8 nM and induces signal transduction events such as mitogen-activated protein kinase (MAP kinase) activation, decrease of cAMP levels, remodeling of the actin cytoskeleton, among others. EDG-1 is a prototypical member of a large family of GPCRs that interact with glycero- and sphingolysolipid phosphates, namely, SPP and lysophosphatidic acid (LPA). Three other GPCRs, trivially termed EDG-3, EDG-5, and EDG-8, are also high-affinity receptors for SPP. The four SPP receptor subtypes regulate different intracellular signal transduction pathways. In vascular endothelial cells, cooperative signaling between EDG-1 and EDG-3 subtypes of SPP receptors results in adherens junction assembly, cell survival, morphogenesis into capillary-like networks, and angiogenesis. SPP acts distinctly, albeit cooperatively, with polypeptide angiogenic factors, resulting in the formation of mature neovessels. Thus SPP signaling as an extracellular mediator via the EDG-1 family of GPCRs may be a heretofore unrecognized mechanism for the regulation of angiogenesis and vascular endothelial cell function.

publication date

  • May 23, 2000

Research

keywords

  • Review

Identity

Language

  • eng

PubMed ID

  • 10818438

Additional Document Info

start page

  • 16

end page

  • 24

volume

  • 905