Sphingosine-1-phosphate signaling via the EDG-1 family of G-protein-coupled receptors.

TitleSphingosine-1-phosphate signaling via the EDG-1 family of G-protein-coupled receptors.
Publication TypeJournal Article
Year of Publication2000
AuthorsHla T, Lee MJ, Ancellin N, Thangada S, Liu CH, Kluk M, Chae SS, Wu MT
JournalAnn N Y Acad Sci
Date Published2000 Apr
KeywordsEvolution, Molecular, GTP-Binding Proteins, Humans, Immediate-Early Proteins, Lysophospholipids, Receptors, Cell Surface, Receptors, G-Protein-Coupled, Receptors, Lysophospholipid, Signal Transduction, Sphingosine

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.

Alternate JournalAnn N Y Acad Sci
PubMed ID10818438
Grant ListDK-45659 / DK / NIDDK NIH HHS / United States
HL-54710 / HL / NHLBI NIH HHS / United States
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Michael Kluk, M.D., Ph.D.

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