title: Pathways of transduction engaged by sphingosine 1-phosphate through G protein-coupled receptors.
abstract: Pathways of transduction employed by receptors for sphingosine 1-phosphate (S1P) are identified by the nature of second messengers and/or downstream targets regulated and, more formally, by direct assays of heterotrimeric G protein activation. The different methods generally agree. S1P1 couples to members of the Gi family, apparently selectively, although reported pertussis toxin (PTX)-insensitive actions make categorical statements regarding exclusivity difficult. S1P2 and S1P3 couple to members of the Gi, Gq, and G12/13 families. S1P4 couples to Gi and possibly G12/13, while S1P5 couples to Gi and G12/13 but not to Gq. In virtually all circumstances, coupling of S1P receptors to Gi is reflected in PTX-sensitive inhibition of adenylyl cyclase, activation of extracellular-regulated kinases (ERKs), and, depending on the cell, activation of phospholipase C (PLC). Coupling to Gq is reflected in PTX-insensitive activation of phospholipase C. Coupling to G12/13 is reflected in activation of Rho and subsequent activation of serum response factor (SRF). Specific linkages have been verified in almost all instances by receptor-promoted [35S]GTPgammaS/GDP exchange on identified G proteins.
authors.affiliation: Department of Pharmacology, School of Medicine, University of Pennsylvania, 3620 Hamilton Walk, Philadelphia, PA 19104-6084, USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: Siehler
authors.forename: David R
authors.initials: DR
authors.lastname: Manning
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000502:physiology; D019204:GTP-Binding Proteins / Q000502:physiology*; D020672:I-kappa B Proteins; D017874:Immediate-Early Proteins / Q000502:physiology; D008246:Lysophospholipids; D000072000:NF-KappaB Inhibitor alpha; D011956:Receptors, Cell Surface / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled; D049312:Receptors, Lysophospholipid; D015398:Signal Transduction / Q000502:physiology*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D017874:Immediate-Early Proteins; D008246:Lysophospholipids; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D049312:Receptors, Lysophospholipid; D000072000:NF-KappaB Inhibitor alpha; C060506:sphingosine 1-phosphate; D019204:GTP-Binding Proteins; D013110:Sphingosine