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
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Calcium / metabolism
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Calcium Signaling / physiology*
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Carbachol / pharmacology
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Cell Line
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Cholinergic Agonists / pharmacology
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DNA-Binding Proteins / metabolism*
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Enzyme Inhibitors / pharmacology
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Genes, Reporter
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Heterotrimeric GTP-Binding Proteins / metabolism*
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Humans
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I-kappa B Proteins*
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Immediate-Early Proteins / metabolism*
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Lysophospholipids*
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NF-KappaB Inhibitor alpha
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NF-kappa B / antagonists & inhibitors
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NF-kappa B / metabolism*
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Protein Kinase C / metabolism
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Receptor, Muscarinic M3
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Receptors, Cell Surface / metabolism*
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Receptors, G-Protein-Coupled*
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Receptors, Lysophospholipid
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Receptors, Muscarinic / metabolism
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Sphingosine / analogs & derivatives*
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Sphingosine / metabolism*
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rho GTP-Binding Proteins / metabolism
Substances
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Cholinergic Agonists
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DNA-Binding Proteins
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Enzyme Inhibitors
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I-kappa B Proteins
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Immediate-Early Proteins
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Lysophospholipids
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NF-kappa B
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NFKBIA protein, human
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Receptor, Muscarinic M3
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Receptors, Cell Surface
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Receptors, G-Protein-Coupled
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Receptors, Lysophospholipid
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Receptors, Muscarinic
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NF-KappaB Inhibitor alpha
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sphingosine 1-phosphate
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Carbachol
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Protein Kinase C
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Heterotrimeric GTP-Binding Proteins
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rho GTP-Binding Proteins
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Sphingosine
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Calcium