Sphingosine 1-phosphate activates nuclear factor-kappa B through Edg receptors. Activation through Edg-3 and Edg-5, but not Edg-1, in human embryonic kidney 293 cells

J Biol Chem. 2001 Dec 28;276(52):48733-9. doi: 10.1074/jbc.M011072200. Epub 2001 Oct 22.

Abstract

Sphingosine 1-phosphate (S1P) exerts a variety of actions as a second messenger or as an agonist that binds to one or more members of the Edg family of G protein-coupled receptors. By using human embryonic kidney 293 cells, we show that S1P activates nuclear factor-kappa B (NF-kappa B) in a receptor-dependent fashion. Edg-3 and Edg-5, which are coupled to G(i), G(q), and G(13), affect activation of NF-kappa B, whereas Edg-1, which is coupled to G(i) alone, does not. We find that the activation of NF-kappa B requires protein kinase C and Ca(2+), probably downstream of G(q), but that the activation of Rho alone by S1P, whether through G(q) or G(13), does not translate into the activation of NF-kappa B. G beta gamma has little effect of its own but potentiates the activation of NF-kappa B achieved through other G proteins. We conclude that the activation of NF-kappa B by S1P is a receptor-mediated process that relies primarily on the activation of a phospholipase C by G(q) and secondarily on effector regulation through other G proteins.

Publication types

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

MeSH terms

  • Calcium / metabolism
  • Calcium Signaling / physiology*
  • Carbachol / pharmacology
  • Cell Line
  • Cholinergic Agonists / pharmacology
  • DNA-Binding Proteins / metabolism*
  • Enzyme Inhibitors / pharmacology
  • Genes, Reporter
  • Heterotrimeric GTP-Binding Proteins / metabolism*
  • Humans
  • I-kappa B Proteins*
  • Immediate-Early Proteins / metabolism*
  • Lysophospholipids*
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism*
  • Protein Kinase C / metabolism
  • Receptor, Muscarinic M3
  • Receptors, Cell Surface / metabolism*
  • Receptors, G-Protein-Coupled*
  • Receptors, Lysophospholipid
  • Receptors, Muscarinic / metabolism
  • Sphingosine / analogs & derivatives*
  • Sphingosine / metabolism*
  • rho GTP-Binding Proteins / metabolism

Substances

  • Cholinergic Agonists
  • DNA-Binding Proteins
  • Enzyme Inhibitors
  • I-kappa B Proteins
  • Immediate-Early Proteins
  • Lysophospholipids
  • NF-kappa B
  • NFKBIA protein, human
  • Receptor, Muscarinic M3
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled
  • Receptors, Lysophospholipid
  • Receptors, Muscarinic
  • NF-KappaB Inhibitor alpha
  • sphingosine 1-phosphate
  • Carbachol
  • Protein Kinase C
  • Heterotrimeric GTP-Binding Proteins
  • rho GTP-Binding Proteins
  • Sphingosine
  • Calcium