Sphingosine-1-phosphate receptor signalling in the heart

Department of Pharmacology, University of California San Diego, School of Medicine, 9500 Gilman Dr., La Jolla, CA 92093-0636, USA

^{Present address: Department of Pharmacology, University of Washington, Seattle, WA 98195, USA.}

^{Corresponding author. Tel: +1 858 822 5858; fax: +1 858 822 0041.}E-mail address: ude.dscu@nworbhj

Department of Pharmacology, University of California San Diego, School of Medicine, 9500 Gilman Dr., La Jolla, CA 92093-0636, USA

Received 2008 Dec 8; Revised 2009 Feb 25; Accepted 2009 Mar 8.

Abstract

The five known members of the sphingosine-1-phosphate (S1P) receptor family exhibit diverse tissue expression profiles and couple to distinct G-protein-mediated signalling pathways. S1P₁, S1P₂, and S1P₃ receptors are all present in the heart, but the ratio of these subtypes differs for various cardiac cells. The goal of this review is to summarize data concerning which S1P receptor subtypes regulate cardiac physiology and pathophysiology, which G-proteins and signalling pathways they couple to, and in which cell types they are expressed. The available information is based on studies using a lamentably limited set of pharmacological agonists/antagonists, but is complemented by work with S1P receptor subtype-specific knockout mice and sphingosine kinase knockout mice. In cardiac myocytes, the S1P₁ receptor subtype is the predominant subtype expressed, and the activation of this receptor inhibits cAMP formation and antagonizes adrenergic receptor-mediated contractility. The S1P₃ receptor, while expressed at lower levels, mediates the bradycardic effect of S1P agonists. Studies using knockout mice indicate that S1P₂ and S1P₃ receptors play a major role in mediating cardioprotection from ischaemia/reperfusion injury in vivo. S1P receptors are also involved in remodelling, proliferation, and differentiation of cardiac fibroblasts, a cell type in which the S1P₃ receptor predominates. Receptors for S1P are also present in endothelial and smooth muscle cells where they mediate peripheral vascular tone and endothelial responses, but the role of this regulatory system in the cardiac vasculature is unknown. Further understanding of the contributions of each cell and receptor subtype to cardiac function and pathophysiology should expedite consideration of the endogenous S1P signalling pathway as a therapeutic target for cardiovascular disease.

Keywords: Sphingosine-1-phosphate receptor, Heart, Myocytes, Knockout mice, Sphingosine-1-phosphate

Abstract

Comparison of S1P receptor subtype expression in various cell types found in the heart. Data for myocytes and fibroblasts are derived from studies of cells isolated from heart; those for vascular endothelium and smooth muscle are based on information from non-cardiac sources. >>, much greater than; >, greater than;=, similar.

References

1. Zhang H, Desai NN, Olivera A, Seki T, Brooker G, Spiegel SSphingosine-1-phosphate, a novel lipid, involved in cellular proliferation. J Cell Biol. 1991;114:155–167.[Google Scholar]
2. Ghosh TK, Bian J, Gill DLIntracellular calcium release mediated by sphingosine derivatives generated in cells. Science. 1990;248:1653–1656.[PubMed][Google Scholar]
3. Payne SG, Milstien S, Spiegel SSphingosine-1-phosphate: dual messenger functions. FEBS Lett. 2002;531:54–57.[PubMed][Google Scholar]
4. Olivera A, Rosenfeldt HM, Bektas M, Wang F, Ishii I, Chun J, et al Sphingosine kinase type 1 Induces G12/13-mediated stress fiber formation yet promotes growth and survival independent of G protein coupled receptors. J Biol Chem. 2003;278:46452–46460.[PubMed][Google Scholar]
5. Chun J, Goetzl EJ, Hla T, Igarashi Y, Lynch KR, Moolenaar W, et al. International Union of Pharmacology. XXXIV. Lysophospholipid Receptor Nomenclature. Pharmacol Rev. 2002;54:265–269.[PubMed]
6. Ishii I, Fukushima N, Ye X, Chun JLysophospholipid receptors: signaling and biology. Annu Rev Biochem. 2004;73:321–354.[PubMed][Google Scholar]
7. Spiegel S, Milstien SSphingosine-1-phosphate: an enigmatic signalling lipid. Nat Rev Mol Cell Biol. 2003;4:397–407.[PubMed][Google Scholar]
8. Lee MJ, Evans M, Hla TThe inducible G protein-coupled receptor edg-1 signals via the G(i)/mitogen-activated protein kinase pathway. J Biol Chem. 1996;271:11272–11279.[PubMed][Google Scholar]
9. Lee MJ, Van Brocklyn JR, Thangada S, Liu CH, Hand AR, Menzeleev R, et al Sphingosine-1-phosphate as a ligand for the G protein-coupled receptor EDG-1. Science. 1998;279:1552–1555.[PubMed][Google Scholar]
10. Zondag GC, Postma FR, Etten IV, Verlaan I, Moolenaar WHSphingosine 1-phosphate signalling through the G-protein-coupled receptor Edg-1. Biochem J. 1998;330:605–609.[Google Scholar]
11. Windh RT, Lee M-J, Hla T, An S, Barr AJ, Manning DRDifferential coupling of the sphingosine 1-phosphate receptors Edg-1, Edg-3, and h218/Edg-5 to the G_i, G_q, and G₁₂ families of heterotrimeric G proteins. J Biol Chem. 1999;274:27351–27358.[PubMed][Google Scholar]
12. Kon J, Sato K, Watanabe T, Tomura H, Kuwabara A, Kimura T, et al Comparison of intrinsic activities of the putative sphingosine 1-phosphate receptor subtypes to regulate several signaling pathways in their cDNA-transfected Chinese hamster ovary cells. J Biol Chem. 1999;274:23940–23947.[PubMed][Google Scholar]
13. Okamoto H, Takuwa N, Yatomi Y, Gonda K, Shigematsu H, Takuwa YEDG3 is a functional receptor specific for sphingosine 1-phosphate and sphingosylphosphorylcholine with signaling characteristics distinct from EDG1 and AGR16. Biochem Biophys Res Commun. 1999;260:203–208.[PubMed][Google Scholar]
14. Van B, Jr, Graler MH, Bernhardt G, Hobson JP, Lipp M, Spiegel SSphingosine-1-phosphate is a ligand for the G protein-coupled receptor EDG-6. Blood. 2000;95:2624–2629.[PubMed][Google Scholar]
15. Yamazaki Y, Kon J, Sato K, Tomura H, Sato M, Yoneya T, et al Edg-6 as a putative sphingosine 1-phosphate receptor coupling to Ca^{signaling pathway.}Biochem Biophys Res Commun. 2000;268:583–589.[PubMed][Google Scholar]
16. Im DS, Heise CE, Ancellin N, O’Dowd BF, Shei GJ, Heavens RP, et al Characterization of a novel sphingosine 1-phosphate receptor, Edg-8. J Biol Chem. 2000;275:14281–14286.[PubMed][Google Scholar]
17. Malek RL, Toman RE, Edsall LC, Wong S, Chiu J, Letterle CA, et al Nrg-1 belongs to the endothelial differentiation gene family of G protein-coupled sphingosine-1-phosphate receptors. J Biol Chem. 2001;276:5692–5699.[PubMed][Google Scholar]
18. Hollinger S, Hepler JRCellular regulation of RGS proteins: modulators and integrators of G protein signaling. Pharmacol Rev. 2002;54:527–559.[PubMed][Google Scholar]
19. Wieland T, Lutz S, Chidiac PRegulators of G protein signalling: a spotlight on emerging functions in the cardiovascular system. Curr Opin Pharmacol. 2007;7:201–207.[PubMed][Google Scholar]
20. Stuebe S, Wieland T, Kraemer E, Stritzky A, Schroeder D, Seekamp S, et al Sphingosine-1-phosphate and endothelin-1 induce the expression of rgs16 protein in cardiac myocytes by transcriptional activation of the rgs16 gene. Naunyn Schmiedebergs Arch Pharmacol. 2008;376:363–373.[PubMed][Google Scholar]
21. Anliker B, Chun JLysophospholipid G protein-coupled receptors. J Biol Chem. 2004;279:20555–20558.[PubMed][Google Scholar]
22. Graler MH, Grosse R, Kusch A, Kremmer E, Gudermann T, Lipp MThe sphingosine 1-phosphate receptor S1P4 regulates cell shape and motility via coupling to Gi and G12/13. J Cell Biochem. 2003;89:507–519.[PubMed][Google Scholar]
23. Zhang J, Honbo N, Goetzl EJ, Chatterjee K, Karliner JS, Gray MOSignals from type 1 sphingosine 1-phosphate receptors enhance adult mouse cardiac myocyte survival during hypoxia. Am J Physiol Heart Circ Physiol. 2007;293:H3150–H3158.[PubMed][Google Scholar]
24. Means CK, Miyamoto S, Chun J, Brown JHS1P1 receptor localization confers selectivity for Gi-mediated cAMP and contractile responses. J Biol Chem. 2008;283:11954–11963.[Google Scholar]
25. Mazurais D, Robert P, Gout B, Berrebi-Bertrand I, Laville MP, Calmels TCell type-specific localization of human cardiac S1P receptors. J Histochem Cytochem. 2002;50:661–670.[PubMed][Google Scholar]
26. Alewijnse AE, Peters SL, Michel MCCardiovascular effects of sphingosine-1-phosphate and other sphingomyelin metabolites. Br J Pharmacol. 2004;143:666–684.[Google Scholar]
27. Chae SS, Proia RL, Hla TConstitutive expression of the S1P1 receptor in adult tissues. Prostaglandins Other Lipid Mediat. 2004;73:141–150.[PubMed][Google Scholar]
28. Liliom K, Sun G, Bunemann M, Virag T, Nusser N, Baker DL, et al Sphingosylphosphocholine is a naturally occurring lipid mediator in blood plasma: a possible role in regulating cardiac function via sphingolipid receptors. Biochem J. 2001;355:189–197.[Google Scholar]
29. Kohama T, Olivera A, Edsall L, Nagiec MM, Dickson R, Spiegel SMolecular cloning and functional characterization of murine sphingosine kinase. J Biol Chem. 1998;273:23722–23728.[PubMed][Google Scholar]
30. Liu H, Sugiura M, Nava VE, Edsall LC, Kono K, Poulton S, et al Molecular cloning and functional characterization of a novel mammalian sphingosine kinase type 2 isoform. J Biol Chem. 2000;275:19513–19520.[PubMed][Google Scholar]
31. Fukuda Y, Kihara A, Igarashi YDistribution of sphingosine kinase activity in mouse tissues: contribution of SPHK1. Biochem Biophys Res Commun. 2003;309:155–160.[PubMed][Google Scholar]
32. Ikeda M, Kihara A, Igarashi YSphingosine-1-phosphate lyase SPL is an endoplasmic reticulum-resident, integral membrane protein with the pyridoxal 5′-phosphate binding domain exposed to the cytosol. Biochem Biophys Res Commun. 2004;325:338–343.[PubMed][Google Scholar]
33. Wendler CC, Rivkees SASphingosine-1-phosphate inhibits cell migration and endothelial to mesenchymal cell transformation during cardiac development. Dev Biol. 2006;291:264–277.[PubMed][Google Scholar]
34. Yatomi Y, Igarashi Y, Yang L, Hisano N, Qi R, Asazuma N, et al Sphingosine 1-phosphate, a bioactive sphingolipid abundantly stored in platelets, is a normal constituent of human plasma and serum. J Biochem (Tokyo) 1997;121:969–973.[PubMed][Google Scholar]
35. Karliner JS, Honbo N, Summers K, Gray MO, Goetzl EJThe lysophospholipids sphingosine-1-phosphate and lysophosphatidic acid enhance survival during hypoxia in neonatal rat cardiac myocytes. J Mol Cell Cardiol. 2001;33:1713–1717.[PubMed][Google Scholar]
36. Graeler MH, Kong Y, Karliner JS, Goetzl EJProtein kinase C epsilon dependence of the recovery from down-regulation of S1P1 G protein-coupled receptors of T lymphocytes. J Biol Chem. 2003;278:27737–27741.[PubMed][Google Scholar]
37. Tao R, Zhang J, Vessey DA, Honbo N, Karliner JSDeletion of the sphingosine kinase-1 gene influences cell fate during hypoxia and glucose deprivation in adult mouse cardiomyocytes. Cardiovasc Res. 2007;74:56–63.[PubMed][Google Scholar]
38. Vessey DA, Li L, Kelley M, Karliner JSCombined sphingosine, S1P and ischemic postconditioning rescue the heart after protracted ischemia. Biochem Biophys Res Commun. 2008;375:425–429.[Google Scholar]
39. Lecour S, Smith RM, Woodward B, Opie LH, Rochette L, Sack MNIdentification of a novel role for sphingolipid signaling in TNF alpha and ischemic preconditioning mediated cardioprotection. J Mol Cell Cardiol. 2002;34:509–518.[PubMed][Google Scholar]
40. Jin ZQ, Zhou HZ, Zhu P, Honbo N, Mochly-Rosen D, Messing RO, et al Cardioprotection mediated by sphingosine-1-phosphate and ganglioside GM-1 in wild-type and PKC epsilon knockout mouse hearts. Am J Physiol Heart Circ Physiol. 2002;282:H1970–H1977.[PubMed][Google Scholar]
41. Jin ZQ, Zhang J, Huang Y, Hoover HE, Vessey DA, Karliner JSA sphingosine kinase 1 mutation sensitizes the myocardium to ischemia/reperfusion injury. Cardiovasc Res. 2007;76:41–50.[PubMed][Google Scholar]
42. Tsukada YT, Sanna MG, Rosen H, Gottlieb RAS1P1-selective agonist SEW2871 exacerbates reperfusion arrhythmias. J Cardiovasc Pharmacol. 2007;50:660–669.[PubMed][Google Scholar]
43. Keul P, Sattler K, Levkau BHDL and its sphingosine-1-phosphate content in cardioprotection. Heart Fail Rev. 2007;12:301–306.[PubMed][Google Scholar]
44. Levkau B, Hermann S, Theilmeier G, van der Giet M, Chun J, Schober O, et al High-density lipoprotein stimulates myocardial perfusion in vivo. Circulation. 2004;110:3355–3359.[PubMed][Google Scholar]
45. Nofer JR, van der Giet M, Tolle M, Wolinska I, von Wnuck LK, Baba HA, et al HDL induces NO-dependent vasorelaxation via the lysophospholipid receptor S1P3. J Clin Invest. 2004;113:569–581.[Google Scholar]
46. Theilmeier G, Schmidt C, Herrmann J, Keul P, Schafers M, Herrgott I, et al High-density lipoproteins and their constituent, sphingosine-1-phosphate, directly protect the heart against ischemia/reperfusion injury in vivo via the S1P3 lysophospholipid receptor. Circ. 2006;114:1403–1409.[PubMed][Google Scholar]
47. Means CK, Xiao CY, Li Z, Zhang T, Omens JH, Ishii I, et al Sphingosine 1-phosphate S1P2 and S1P3 receptor-mediated Akt activation protects against in vivo myocardial ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol. 2007;292:H2944–H2951.[PubMed][Google Scholar]
48. Jones SP, Greer JJ, van Haperen R, Duncker DJ, de Crom R, Lefer DJEndothelial nitric oxide synthase overexpression attenuates congestive heart failure in mice. Proc Natl Acad Sci USA. 2003;100:4891–4896.[Google Scholar]
49. Jones SP, Girod WG, Palazzo AJ, Granger DN, Grisham MB, Jourd’Heuil D, et al Myocardial ischemia-reperfusion injury is exacerbated in absence of endothelial cell nitric oxide synthase. Am J Physiol. 1999;276:H1567–H1573.[PubMed][Google Scholar]
50. Jones S, Greer JJ, Kakkar AK, Ware PD, Turnage RH, Hicks M, et al Endothelial nitric oxide synthase overexpression attenuates myocardial reperfusion injury. Am J Physiol Heart Circ Physiol. 2004;286:H276–H282.[PubMed][Google Scholar]
51. Liu Y, Wada R, Yamashita H, Mi Y, Deng C-X, Hobson JP, et al Edg-1, the G protein-coupled receptor for sphingosine-1-phosphate, is essential for vascular maturation. J Clin Invest. 2000;106:951–961.[Google Scholar]
52. Hilal-Dandan R, Means CK, Gustafsson AB, Morissette MR, Adams JW, Brunton LL, et al Lysophosphatidic acid induces hypertrophy of neonatal cardiac myocytes via activation of Gi and Rho. J Mol Cell Cardiol. 2004;36:481–493.[PubMed][Google Scholar]
53. Goetzl EJ, Lee H, Azuma T, Stossel TP, Turck CW, Karliner JSGelsolin binding and cellular presentation of lysophosphatidic acid. J Biol Chem. 2000;275:14573–14578.[PubMed][Google Scholar]
54. Sekiguchi K, Yokoyama T, Kurabayashi M, Okajima F, Nagai RSphingosylphosphorylcholine induces a hypertrophic growth response through the mitogen-activated protein kinase signaling cascade in rat neonatal cardiac myocytes. Circ Res. 1999;85:1000–1008.[PubMed][Google Scholar]
55. Robert P, Tsui P, Laville MP, Livi GP, Sarau HM, Bril A, et al Edg1 receptor stimulation leads to cardiac hypertrophy in rat neonatal myocytes. J Mol Cell Cardiol. 2001;33:1589–1606.[PubMed][Google Scholar]
56. Wei LLysophospholipid signaling in cardiac myocyte hypertrophy. J Mol Cell Cardiol. 2004;36:465–468.[PubMed][Google Scholar]
57. Ishii I, Friedman B, Ye X, Kawamura S, McGiffert C, Contos JJ, et al Selective loss of sphingosine 1-phosphate signaling with no obvious phenotypic abnormality in mice lacking its G protein-coupled receptor, LP(B3)/EDG-3. J Biol Chem. 2001;276:33697–33704.[PubMed][Google Scholar]
58. Dorn GW, Tepe NM, Lorenz JW, Koch WJ, Liggett SBLow- and high-level transgenic expression of β₂-adrenergic receptors differentially affect cardiac hypertrophy and function in Gα_q-overexpressing mice. Proc Natl Acad Sci USA. 1999;96:6400–6405.[Google Scholar]
59. Wettschureck N, Rutten H, Zywietz A, Gehring D, Wilkie TM, Chen J, et al Absence of pressure overload induced myocardial hypertrophy after conditional inactivation of Galphaq/Galpha11 in cardiomyocytes. Nat Med. 2001;7:1236–1240.[PubMed][Google Scholar]
60. Sugiyama A, Aye NN, Yatomi Y, Ozaki Y, Hashimoto KEffects of sphingosine 1-phosphate, a naturally occurring biologically active lysophospholipid, on the rat cardiovascular system. Jpn J Pharmacol. 2000;82:338–342.[PubMed][Google Scholar]
61. Sugiyama A, Yatomi Y, Ozaki Y, Hashimoto KSphingosine 1-phosphate induces sinus tachycardia and coronary vasoconstriction in the canine heart. Cardiovasc Res. 2000;46:119–125.[PubMed][Google Scholar]
62. Bunemann M, Brandts B, zu Heringdorf DM, van Koppen CJ, Jakobs KH, Pott LActivation of muscarinic K^{current in guinea-pig atrial myocytes by sphingosine-1-phosphate.}J Physiol. 1995;489:701–777.[Google Scholar]
63. Bunemann M, Liliom K, Brandts BK, Pott L, Tseng JL, Desiderio DM, et al A novel membrane receptor with high affinity for lysosphingomyelin and sphingosine 1-phosphate in atrial myocytes. EMBO J. 1996;15:5527–5534.[Google Scholar]
64. Ochi R, Momose Y, Oyama K, Giles WRSphingosine-1-phosphate effects on guinea pig atrial myocytes: alterations in action potentials and K+ currents. Cardiovasc Res. 2006;70:88–96.[PubMed][Google Scholar]
65. Guo J, MacDonell KL, Giles WREffects of sphingosine 1-phosphate on pacemaker activity in rabbit sino-atrial node cells. Pflugers Arch. 1999;438:642–648.[PubMed][Google Scholar]
66. Himmel HM, Meyer zu HD, Graf E, Dobrev D, Kortner A, Schuler S, et al Evidence for Edg-3 receptor-mediated activation of I(K.ACh) by sphingosine-1-phosphate in human atrial cardiomyocytes. Mol Pharmacol. 2000;58:449–454.[PubMed][Google Scholar]
67. Ancellin N, Hla TDifferential pharmacological properties and signal transduction of the sphingosine 1-phosphate receptors EDG-1, EDG-3, and EDG-5. J Biol Chem. 1999;274:18997–19002.[PubMed][Google Scholar]
68. Voogd TE, Vansterkenburg EL, Wilting J, Janssen LHRecent research on the biological activity of suramin. Pharmacol Rev. 1993;45:177–203.[PubMed][Google Scholar]
69. Sanna MG, Liao J, Jo E, Alfonso C, Ahn MY, Peterson MS, et al Sphingosine 1-phosphate (S1P) receptor subtypes S1P1 and S1P3, respectively, regulate lymphocyte recirculation and heart rate. J Biol Chem. 2004;279:13839–13848.[PubMed][Google Scholar]
70. Forrest M, Sun SY, Hajdu R, Bergstrom J, Card D, Doherty G, et al Immune cell regulation and cardiovascular effects of sphingosine 1-phosphate receptor agonists in rodents are mediated via distinct receptor subtypes. J Pharmacol Exp Ther. 2004;309:758–768.[PubMed][Google Scholar]
71. Budde K, Schmouder RL, Brunkhorst R, Nashan B, Lucker PW, Mayer T, et al First human trial of FTY720, a novel immunomodulator, in stable renal transplant patients. J Am Soc Nephrol. 2002;13:1073–1083.[PubMed][Google Scholar]
72. Budde K, Schutz M, Glander P, Peters H, Waiser J, Liefeldt L, et al FTY720 (fingolimod) in renal transplantation. Clin Transplant. 2006;20(Suppl. 17):17–24.[PubMed][Google Scholar]
73. Martini S, Peters H, Bohler T, Budde KCurrent perspectives on FTY720. Expert Opin Investig Drugs. 2007;16:505–518.[PubMed][Google Scholar]
74. Landeen LK, Dederko DA, Kondo CS, Hu BS, Aroonsakool N, Haga JH, et al Mechanisms of the negative inotropic effects of sphingosine-1-phosphate on adult mouse ventricular myocytes. Am J Physiol Heart Circ Physiol. 2008;294:H736–H749.[PubMed][Google Scholar]
75. Igarashi J, Michel T. Agonist-modulated targeting of the EDG-1 receptor to plasmalemmal caveolae. eNOS transactivation by sphingosine 1-phosphate and the role of caveolin-1 in sphingolipid signal transduction. J Biol Chem. 2000;275:32363–32370.[PubMed]
76. Shaul PW, Anderson RGWRole of plasmalemmal caveolae in signal transduction. Am J Physiol. 1998;275:L843–L851.[PubMed][Google Scholar]
77. Pike LJLipid rafts: bringing order to chaos. J Lipid Res. 2003;44:655–667.[PubMed][Google Scholar]
78. Ostrom RS, Insel PAThe evolving role of lipid rafts and caveolae in G protein-coupled receptor signaling: implications for molecular pharmacology. Br J Pharmacol. 2004;143:235–245.[Google Scholar]
79. Osborne N, Stainier DYLipid receptors in cardiovascular development. Annu Rev Physiol. 2003;65:23–43.[PubMed][Google Scholar]
80. McVerry BJ, Garcia JGEndothelial cell barrier regulation by sphingosine 1-phosphate. J Cell Biochem. 2004;92:1075–1085.[PubMed][Google Scholar]
81. Kimura T, Watanabe T, Sato K, Kon J, Tomura H, Tamama K, et al Sphingosine 1-phosphate stimulates proliferation and migration of human endothelial cells possibly through the lipid receptors, Edg-1 and Edg-3. Biochem J. 2000;348:71–76.[Google Scholar]
82. Osada M, Yatomi Y, Ohmori T, Ikeda H, Ozaki YEnhancement of sphingosine 1-phosphate-induced migration of vascular endothelial cells and smooth muscle cells by an EDG-5 antagonist. Biochem Biophys Res Commun. 2002;299:483–487.[PubMed][Google Scholar]
83. Allende ML, Yamashita T, Proia RLG-protein-coupled receptor S1P1 acts within endothelial cells to regulate vascular maturation. Blood. 2003;102:3665–3667.[PubMed][Google Scholar]
84. Kluk MJ, Hla TSignaling of sphingosine-1-phosphate via the S1P/EDG-family of G-protein-coupled receptors. Biochim Biophys Acta. 2002;1582:72–80.[PubMed][Google Scholar]
85. Wang F, Van Brocklyn JR, Hobson JP, Movafagh S, Zukowska-Grojec Z, Milstien S, et al. Sphingosine 1-phosphate stimulates cell migration through a G(i)-coupled cell surface receptor. Potential involvement in angiogenesis. J Biol Chem. 1999;274:35343–35350.[PubMed]
86. Lee MJ, Thangada S, Claffey KP, Ancellin N, Liu CH, Kluk M, et al Vascular endothelial cell adherens junction assembly and morphogenesis induced by sphingosine-1-phosphate. Cell. 1999;99:301–312.[PubMed][Google Scholar]
87. Michel MC, Mulders AC, Jongsma M, Alewijnse AE, Peters SLVascular effects of sphingolipids. Acta Paediatr Suppl. 2007;96:44–48.[PubMed][Google Scholar]
88. Ohmori T, Yatomi Y, Okamoto H, Miura Y, Rile G, Satoh K, et al G(i)-mediated Cas tyrosine phosphorylation in vascular endothelial cells stimulated with sphingosine 1-phosphate: possible involvement in cell motility enhancement in cooperation with Rho-mediated pathways. J Biol Chem. 2001;276:5274–5280.[PubMed][Google Scholar]
89. Licht T, Tsirulnikov L, Reuveni H, Yarnitzky T, Ben-Sasson SAInduction of pro-angiogenic signaling by a synthetic peptide derived from the second intracellular loop of S1P3 (EDG3) Blood. 2003;102:2099–2107.[PubMed][Google Scholar]
90. English D, Brindley DN, Spiegel S, Garcia JGLipid mediators of angiogenesis and the signalling pathways they initiate. Biochim Biophys Acta. 2002;1582:228–239.[PubMed][Google Scholar]
91. Schaphorst KL, Chiang E, Jacobs KN, Zaiman A, Natarajan V, Wigley F, et al Role of sphingosine-1 phosphate in the enhancement of endothelial barrier integrity by platelet-released products. Am J Physiol Lung Cell Mol Physiol. 2003;285:L258–L267.[PubMed][Google Scholar]
92. Garcia JG, Liu F, Verin AD, Birukova A, Dechert MA, Gerthoffer WT, et al Sphingosine 1-phosphate promotes endothelial cell barrier integrity by Edg-dependent cytoskeletal rearrangement. J Clin Invest. 2001;108:689–701.[Google Scholar]
93. Kluk MJ, Hla TRole of the sphingosine 1-phosphate receptor EDG-1 in vascular smooth muscle cell proliferation and migration. Circ Res. 2001;89:496–502.[PubMed][Google Scholar]
94. Sanchez T, Skoura A, Wu MT, Casserly B, Harrington EO, Hla TInduction of vascular permeability by the sphingosine-1-phosphate receptor-2 (S1P2R) and its downstream effectors ROCK and PTEN. Arterioscler Thromb Vasc Biol. 2007;27:1312–1318.[PubMed][Google Scholar]
95. Ishii I, Ye X, Friedman B, Kawamura S, Contos JJ, Kingsbury MA, et al Marked perinatal lethality and cellular signaling deficits in mice null for the two sphingosine 1-phosphate (S1P) receptors, S1P₂/LP_B2/EDG-5 and S1P₃/LP_B3/EDG-3. J Biol Chem. 2002;277:25152–25159.[PubMed][Google Scholar]
96. Takuwa YSubtype-specific differential regulation of Rho family G proteins and cell migration by the Edg family sphingosine-1-phosphate receptors. Biochim Biophys Acta. 2002;1582:112–120.[PubMed][Google Scholar]
97. Ryu Y, Takuwa N, Sugimoto N, Sakurada S, Usui S, Okamoto H, et al Sphingosine-1-phosphate, a platelet-derived lysophospholipid mediator, negatively regulates cellular Rac activity and cell migration in vascular smooth muscle cells. Circ Res. 2002;90:325–332.[PubMed][Google Scholar]
98. Salomone S, Potts EM, Tyndall S, Ip PC, Chun J, Brinkmann V, et al Analysis of sphingosine 1-phosphate receptors involved in constriction of isolated cerebral arteries with receptor null mice and pharmacological tools. Br J Pharmacol. 2008;153:140–147.[Google Scholar]
99. Mulders AC, Hendriks-Balk MC, Mathy MJ, Michel MC, Alewijnse AE, Peters SLSphingosine kinase-dependent activation of endothelial nitric oxide synthase by angiotensin II. Arterioscler Thromb Vasc Biol. 2006;26:2043–2048.[PubMed][Google Scholar]
100. Igarashi J, Michel TS1P and eNOS regulation. Biochim Biophys Acta. 2008;1781:489–495.[PubMed][Google Scholar]
101. Lorenz JN, Arend LJ, Robitz R, Paul RJ, MacLennan AJVascular dysfunction in S1P2 sphingosine 1-phosphate receptor knockout mice. Am J Physiol Regul Integr Comp Physiol. 2007;292:R440–R446.[PubMed][Google Scholar]
102. Kacimi R, Vessey DA, Honbo N, Karliner JSAdult cardiac fibroblasts null for sphingosine kinase-1 exhibit growth dysregulation and an enhanced proinflammatory response. J Mol Cell Cardiol. 2007;43:85–91.[PubMed][Google Scholar]
103. Lowe NG, Swaney JS, Moreno KM, Sabbadini RASphingosine-1-phosphate and sphingosine kinase are critical for TGF-β-stimulated collagen production by cardiac fibroblasts. Cardiovasc Res. 2009;82:303–312.[Google Scholar]
104. Wang F, Nobes CD, Hall A, Spiegel SSphingosine 1-phosphate stimulates Rho-mediated tyrosine phosphorylation of focal adhesion kinase and paxillin in Swiss 3T3 fibroblasts. Biochem J. 1997;324:481–488.[Google Scholar]
105. Olivera A, Kohama T, Edsall L, Nava V, Cuvillier O, Poulton S, et al Sphingosine kinase expression increases intracellular sphingosine-1-phosphate and promotes cell growth and survival. J Cell Biol. 1999;147:545–548.[Google Scholar]
106. Urata Y, Nishimura Y, Hirase T, Yokoyama MSphingosine 1-phosphate induces alpha-smooth muscle actin expression in lung fibroblasts via Rho-kinase. Kobe J Med Sci. 2005;51:17–27.[PubMed][Google Scholar]
107. Serriere-Lanneau V, Teixeira-Clerc F, Li L, Schippers M, de Wries W, Julien B, et al The sphingosine 1-phosphate receptor S1P2 triggers hepatic wound healing. FASEB J. 2007;21:2005–2013.[PubMed][Google Scholar]
108. Park HY, Youm JK, Kwon MJ, Park BD, Lee SH, Choi EHK6PC-5, a novel sphingosine kinase activator, improves long-term ultraviolet light-exposed aged murine skin. Exp Dermatol. 2008;17:829–836.[PubMed][Google Scholar]