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Sphingosine Kinase: Biochemical and Cellular Regulation and Role in Disease

  • Taha, Tarek Assad (Department of Medicine, Medical University of South Carolina) ;
  • Hannun, Yusuf Awni (Department of Biochemistry and Molecular Biology, Medical University of South Carolina) ;
  • Obeid, Lina Marie (Department of Medicine, Medical University of South Carolina)
  • Received : 2006.01.24
  • Published : 2006.03.31

Abstract

Sphingolipids have emerged as molecules whose metabolism is regulated leading to generation of bioactive products including ceramide, sphingosine, and sphingosine-1-phosphate. The balance between cellular levels of these bioactive products is increasingly recognized to be critical to cell regulation; whereby, ceramide and sphingosine cause apoptosis and growth arrest phenotypes, and sphingosine-1-phosphate mediates proliferative and angiogenic responses. Sphingosine kinase is a key enzyme in modulating the levels of these lipids and is emerging as an important and regulated enzyme. This review is geared at mechanisms of regulation of sphingosine kinase and the coming to light of its role in disease.

Keywords

References

  1. Alemany, R., Kleuser, B., Ruwisch, L., Danneberg, K., Lass, H., Hashemi, R., Spiegel, S., Jakobs, K. H. and Meyer zu Heringdorf, D. (2001) Depolarisation induces rapid and transient formation of intracellular sphingosine-1-phosphate. FEBS Lett. 509, 239-244 https://doi.org/10.1016/S0014-5793(01)03168-4
  2. Alemany, R., Sichelschmidt, B., zu Heringdorf, D. M., Lass, H., van Koppen, C. J. and Jakobs, K. H. (2000) Stimulation of sphingosine-1-phosphate formation by the P2Y(2) receptor in HL-60 cells: Ca(2+) requirement and implication in receptormediated Ca(2+) mobilization, but not MAP kinase activation. Mol. Pharmacol. 58, 491-497 https://doi.org/10.1124/mol.58.3.491
  3. Allende, M. L., Sasaki, T., Kawai, H., Olivera, A., Mi, Y., van Echten-Deckert, G., Hajdu, R., Rosenbach, M., Keohane, C. A., Mandala, S., Spiegel, S. and Proia, R. L. (2004) Mice deficient in sphingosine kinase 1 are rendered lymphopenic by FTY720. J. Biol. Chem. 279, 52487-52492 https://doi.org/10.1074/jbc.M406512200
  4. Argraves, K. M., Wilkerson, B. A., Argraves, W. S., Fleming, P. A., Obeid, L. M. and Drake, C. J. (2004) Sphingosine-1- phosphate signaling promotes critical migratory events in vasculogenesis. J. Biol. Chem. 279, 50580-50590 https://doi.org/10.1074/jbc.M404432200
  5. Ancellin, N., Colmont, C., Su, J., Li, Q., Mittereder, N., Chae, S. S., Stefansson, S., Liau, G. and Hla, T. (2002) Extracellular export of sphingosine kinase-1 enzyme. Sphingosine 1- phosphate generation and the induction of angiogenic vascular maturation. J. Biol. Chem. 277, 6667-6675 https://doi.org/10.1074/jbc.M102841200
  6. Auge, N., Nikolova-Karakashian, M., Carpentier, S., Parthasarathy, S., Negre-Salvayre, A., Salvayre, R., Merrill, A. H. Jr. and Levade, T. (1999) Role of sphingosine 1-phosphate in the mitogenesis induced by oxidized low density lipoprotein in smooth muscle cells via activation of sphingomyelinase, ceramidase, and sphingosine kinase. J. Biol. Chem. 274, 21533- 21538 https://doi.org/10.1074/jbc.274.31.21533
  7. Banno, Y., Kato, M., Hara, A. and Nozawa, Y. (1998) Evidence for the presence of multiple forms of Sph kinase in human platelets. Biochem. J. 335, 301-304 https://doi.org/10.1042/bj3350301
  8. Baumruker, T., Bornancin, F. and Billich, A. (2005) The role of sphingosine and ceramide kinases in inflammatory responses. Immunol. Lett. 96, 175-185 https://doi.org/10.1016/j.imlet.2004.09.001
  9. Bektas, M., Jolly, P. S., Muller, C., Eberle, J., Spiegel, S. and Geilen, C. C. (2005) Sphingosine kinase activity counteracts ceramide-mediated cell death in human melanoma cells: role of Bcl-2 expression. Oncogene 24, 178-187 https://doi.org/10.1038/sj.onc.1208019
  10. Billich, A., Bornancin, F., Devay, P., Mechtcheriakova, D., Urtz, N. and Baumruker, T. (2003) Phosphorylation of the immunomodulatory drug FTY720 by sphingosine kinases. J. Biol. Chem. 278, 47408-47415 https://doi.org/10.1074/jbc.M307687200
  11. Blom, T., Slotte, J. P., Pitson, S. M. and Tornquist, K. (2005) Enhancement of intracellular sphingosine-1-phosphate production by inositol 1,4,5-trisphosphate-evoked calcium mobilisation in HEK-293 cells: endogenous sphingosine-1-phosphate as a modulator of the calcium response. Cell Signal 17, 827-836 https://doi.org/10.1016/j.cellsig.2004.11.022
  12. Brinkmann, V. and Lynch, K. R. (2002) FTY720: targeting Gprotein- coupled receptors for sphingosine 1-phosphate in transplantation and autoimmunity. Curr. Opin. Immunol. 14, 569-575 https://doi.org/10.1016/S0952-7915(02)00374-6
  13. Brinkmann, V., Pinschewer, D. D., Feng, L. and Chen, S. (2001) FTY720: altered lymphocyte traffic results in allograft protection. Transplantation 72, 764-769 https://doi.org/10.1097/00007890-200109150-00002
  14. Brinkmann, V., Chen, S., Feng, L., Pinschewer, D., Nikolova, Z. and Hof, R. (2001) FTY720 alters lymphocyte homing and protects allografts without inducing general immunosuppression. Transplant Proc. 33, 530-531 https://doi.org/10.1016/S0041-1345(00)02126-6
  15. Brinkmann, V., Cyster, J. G. and Hla, T. (2004) FTY720: sphingosine 1-phosphate receptor-1 in the control of lymphocyte egress and endothelial barrier function. Am. J. Transplant. 4, 1019-1025 https://doi.org/10.1111/j.1600-6143.2004.00476.x
  16. Brinkmann, V., Pinschewer, D., Chiba, K. and Feng, L. (2000) FTY720: a novel transplantation drug that modulates lymphocyte traffic rather than activation. Trends Pharmacol. Sci. 21, 49-52 https://doi.org/10.1016/S0165-6147(99)01419-4
  17. Buehrer, B. M., Bardes, E. S. and Bell, R. M. (1996) Protein kinase C-dependent regulation of human erythroleukemia (HEL) cell sphingosine kinase activity. Biochim. Biophys. Acta. 1303, 233-242 https://doi.org/10.1016/0005-2760(96)00092-6
  18. Buehrer, B. M. and Bell, R. M. (1992) Inhibition of sphingosine kinase in vitro and in platelets. Implications for signal transduction pathways. J. Biol. Chem. 267, 3154-3159
  19. Chae, S. S., Paik, J. H., Furneaux, H. and Hla, T. (2004) Requirement for sphingosine 1-phosphate receptor-1 in tumor angiogenesis demonstrated by in vivo RNA interference. J. Clin. Invest. 114, 1082-1089 https://doi.org/10.1172/JCI200422716
  20. Chen, S., Bacon, K. B., Garcia, G., Liao, R., Pan, Z. K., Sullivan, S. K., Nakano, H., Matsuzawa, A., Brinkmann, V. and Feng, L. (2001) FTY720, a novel transplantation drug, modulates lymphocyte migratory responses to chemokines. Transplant Proc. 33, 3057-3063 https://doi.org/10.1016/S0041-1345(01)02306-5
  21. Chen, X. L., Grey, J. Y., Thomas, S., Qiu, F. H., Medford, R. M., Wasserman, M. A. and Kunsch, C. (2004) Sphingosine kinase- 1 mediates TNF-alpha-induced MCP-1 gene expression in endothelial cells: upregulation by oscillatory flow. Am. J. Physiol. Heart Circ. Physiol. 287, H1452-1458 https://doi.org/10.1152/ajpheart.01101.2003
  22. Chin, T.-Y., Hwang, H.-M. and Chueh, S.-H. (2002) Distinct effects of different calcium-mobilizing agents on cell death in NG108-15 neuroblastoma X glioma cells. Mol. Pharmacol. 61, 486-494 https://doi.org/10.1124/mol.61.3.486
  23. Chiba, K., Yanagawa, Y., Masubuchi, Y., Kataoka, H., Kawaguchi, T., Ohtsuki, M. and Hoshino, Y. (1998) FTY720, a novel immunosuppressant, induces sequestration of circulating mature lymphocytes by acceleration of lymphocyte homing in rats. I. FTY720 selectively decreases the number of circulating mature lymphocytes by acceleration of lymphocyte homing. J. Immunol. 160, 5037-5044
  24. Choi, O. H., Kim, J. H. and Kinet, J. P. (1996) Calcium mobilization via sphingosine kinase in signalling by the Fc epsilon RI antigen receptor. Nature 380, 634-636 https://doi.org/10.1038/380634a0
  25. Cinamon, G., Matloubian, M., Lesneski, M. J., Xu, Y., Low, C., Lu, T., Proia, R. L. and Cyster, J. G. (2004) Sphingosine 1- phosphate receptor 1 promotes B cell localization in the splenic marginal zone. Nat. Immunol. 5, 713-720 https://doi.org/10.1038/ni1083
  26. Coursol, S., Fan, L. M., Le Stunff, H., Spiegel, S., Gilroy, S. and Assmann, S. M. (2003) Sphingolipid signalling in Arabidopsis guard cells involves heterotrimeric G proteins. Nature 423, 651-654 https://doi.org/10.1038/nature01643
  27. Cummings, R. J., Parinandi, N. L., Zaiman, A., Wang, L., Usatyuk, P. V., Garcia, J. G. and Natarajan, V. (2002) Phospholipase D activation by sphingosine 1-phosphate regulates interleukin-8 secretion in human bronchial epithelial cells. J. Biol. Chem. 277, 30227-30235 https://doi.org/10.1074/jbc.M111078200
  28. Cuvillier, O., Pirianov, G., Kleuser, B., Vanek, P. G., Coso, O. A., Gutkind, S. and Spiegel, S. (1996) Suppression of ceramidemediated programmed cell death by sphingosine-1-phosphate. Nature 381, 800-803 https://doi.org/10.1038/381800a0
  29. Delon, C., Manifava, M., Wood, E., Thompson, D., Krugmann, S., Pyne, S. and Ktistakis, N. T. (2004) Sphingosine kinase 1 is an intracellular effector of phosphatidic acid. J. Biol. Chem. 279, 44763-44774 https://doi.org/10.1074/jbc.M405771200
  30. Deutschman, D. H., Carstens, J. S., Klepper, R. L., Smith, W. S., Page, M. T., Young, T. R., Gleason, L. A., Nakajima, N. and Sabbadini, R. A. (2003) Predicting obstructive coronary artery disease with serum sphingosine-1-phosphate. Am. Heart J. 146, 62-68 https://doi.org/10.1016/S0002-8703(03)00118-2
  31. Edsall, L. C., Pirianov, G. G. and Spiegel, S. (1997) Involvement of sphingosine 1-phosphate in nerve growth factor-mediated neuronal survival and differentiation. J. Neurosci. 17, 6952- 6960 https://doi.org/10.1523/JNEUROSCI.17-18-06952.1997
  32. Endo, K., Igarashi, Y., Nisar, M., Zhou, Q. H. and Hakomori, S. (1991) Cell membrane signaling as target in cancer therapy: inhibitory effect of N,N-dimethyl and N,N,N-trimethyl sphingosine derivatives on in vitro and in vivo growth of human tumor cells in nude mice. Cancer Res. 51, 1613-1618
  33. English, D., Welch, Z., Kovala, A. T., Harvey, K., Volpert, O. V., Brindley, D. N. and Garcia, J. G. (2000) Sphingosine 1- phosphate released from platelets during clotting accounts for the potent endothelial cell chemotactic activity of blood serum and provides a novel link between hemostasis and angiogenesis. FASEB J. 14, 2255-2265 https://doi.org/10.1096/fj.00-0134com
  34. Feistritzer, C. and Riewald, M. (2004) Endothelial barrier protection by activated protein C through PAR1-dependent sphingosine 1-phosphate receptor-1 crossactivation. Blood 105, 3178-3184 https://doi.org/10.1182/blood-2004-10-3985
  35. Forrest, M., Sun, S. Y., Hajdu, R., Bergstrom, J., Card, D., Doherty, G., Hale, J., Keohane, C., Meyers, C., Milligan, J., Mills, S., Nomura, N., Rosen, H., Rosenbach, M., Shei, G. J., Singer, I. I., Tian, M., West, S., White, V., Xie, J., Proia, R. L. and Mandala, S. (2004) Immune cell regulation and cardiovascular effects of sphingosine 1-phosphate receptor agonists in rodents are mediated via distinct receptor subtypes. J. Pharmacol. Exp. Ther. 309, 758-768 https://doi.org/10.1124/jpet.103.062828
  36. French, K. J., Schrecengost, R. S., Lee, B. D., Zhuang, Y., Smith, S. N., Eberly, J. L., Yun, J. K. and Smith, C. D. (2003) Discovery and evaluation of inhibitors of human sphingosine kinase. Cancer Res. 63, 5962-5969
  37. Fukuda, Y., Kihara, A. and Igarashi, Y. (2003) Distribution of sphingosine kinase activity in mouse tissues: contribution of SPHK1. Biochem. Biophys. Res. Commun. 309, 155-160 https://doi.org/10.1016/S0006-291X(03)01551-1
  38. Fukuda, Y., Aoyama, Y., Wada, A. and Igarashi, Y. (2004) Identification of PECAM-1 association with sphingosine kinase 1 and its regulation by agonist-induced phosphorylation. Biochim. Biophys. Acta. 1636, 12-21 https://doi.org/10.1016/j.bbalip.2003.11.006
  39. Fukushima, N., Ishii, I., Contos, J. J., Weiner, J. A. and Chun, J. (2001) Lysophospholipid receptors. Annu. Rev. Pharmacol. Toxicol. 41, 507-534 https://doi.org/10.1146/annurev.pharmtox.41.1.507
  40. Funato, K., Lombardi, R., Vallee, B. and Riezman, H. (2003) Lcb4p is a key regulator of ceramide synthesis from exogenous long chain sphingoid base in Saccharomyces cerevisiae. J. Biol. Chem. 278, 7325-7334 https://doi.org/10.1074/jbc.M209925200
  41. Gijsbers, S., Van der Hoeven, G. and Van Veldhoven, P. P. (2001) Subcellular study of s phingoid base phosphorylation in rat tissues: evidence for multiple sphingosine kinases. Biochim. Biophys. Acta. 1532, 37-50 https://doi.org/10.1016/S1388-1981(01)00111-1
  42. Garcia, J. G., Liu, F., Verin, A. D., Birukova, A., Dechert, M. A., Gerthoffer, W. T., Bamberg, J. R. and English, D. (2001) Sphingosine 1-phosphate promotes endothelial cell barrier integrity by Edg-dependent cytoskeletal rearrangement. J. Clin. Invest. 108, 689-701 https://doi.org/10.1172/JCI12450
  43. Gennero, I., Fauvel, J., Nieto, M., Cariven, C., Gaits, F., Briand- Mesange, F., Chap, H. and Salles, J. P. (2002) Apoptotic effect of sphingosine 1-phosphate and increased sphingosine 1- phosphate hydrolysis on mesangial cells cultured at low cell density. J. Biol. Chem. 277, 12724-12734 https://doi.org/10.1074/jbc.M108933200
  44. Geoffroy, K., Troncy, L., Wiernsperger, N., Lagarde, M. and El Bawab, S. (2005) Glomerular proliferation during early stages of diabetic nephropathy is associated with local increase of sphingosine-1-phosphate levels. FEBS Lett. 579, 1249-1254 https://doi.org/10.1016/j.febslet.2004.12.094
  45. Graeler, M. and Goetzl, E. J. (2002) Activation-regulated expression and chemotactic function of sphingosine 1- phosphate receptors in mouse splenic T cells. FASEB J. 16, 1874-1878 https://doi.org/10.1096/fj.02-0548com
  46. Hait, N. C., Fujita, K., Lester, R. L. and Dickson, R. C. (2002) Lcb4p sphingoid base kinase localizes to the Golgi and late endosomes. FEBS Lett. 532, 97-102 https://doi.org/10.1016/S0014-5793(02)03636-0
  47. Hannun, Y. A., Luberto, C. and Argraves, K. M. (2001) Enzymes of sphingolipid metabolism: from modular to integrative signaling. Biochemistry 40, 4893-4903 https://doi.org/10.1021/bi002836k
  48. Hayashi, S., Okada, T., Igarashi, N., Fujita, T., Jahangeer, S. and Nakamura, S. (2002) Identification and characterization of RPK118, a novel sphingosine kinase-1-binding protein. J. Biol. Chem. 277, 33319-33324 https://doi.org/10.1074/jbc.M201442200
  49. Henning, G., Ohl, L., Junt, T., Reiterer, P., Brinkmann, V., Nakano, H., Hohenberger, W., Lipp, M. and Forster, R. (2001) CC chemokine receptor 7-dependent and -independent pathways for lymphocyte homing: modulation by FTY720. J. Exp. Med. 194, 1875-1881 https://doi.org/10.1084/jem.194.12.1875
  50. Herr, D. R., Fyrst, H., Creason, M. B., Phan, V. H., Saba, J. D. and Harris, G. L. (2004) Characterization of the Drosophila sphingosine kinases and requirement for Sk2 in normal reproductive function. J. Biol. Chem. 279, 12685-12694 https://doi.org/10.1074/jbc.M310647200
  51. Hirschberg, C. B., Kisic, A. and Schroepfer, G. J., Jr. (1970) Enzymatic formation of dihydrosphingosine l-phosphate. J. Biol. Chem. 245, 3084-3090
  52. Hla, T. (2004) Physiological and pathological actions of sphingosine 1-phosphate. Semin. Cell Dev. Biol. 15, 513-520 https://doi.org/10.1016/j.semcdb.2004.05.002
  53. Hla, T., Lee, M. J., Ancellin, N., Paik, J. H. and Kluk, M. J. (2001) Lysophospholipids--receptor revelations. Science 294, 1875-1878 https://doi.org/10.1126/science.1065323
  54. Hobson, J. P., Rosenfeldt, H. M., Barak, L. S., Olivera, A., Poulton, S., Caron, M. G., Milstien, S. and Spiegel, S. (2001) Role of the sphingosine-1-phosphate receptor EDG-1 in PDGF-induced cell motility. Science 291, 1800-1803 https://doi.org/10.1126/science.1057559
  55. Hong, G., Baudhuin, L. M. and Xu, Y. (1999) Sphingosine-1- phosphate modulates growth and adhesion of ovarian cancer cells. FEBS Lett. 460, 513-518 https://doi.org/10.1016/S0014-5793(99)01400-3
  56. Honig, S. M., Fu, S., Mao, X., Yopp, A., Gunn, M. D., Randolph, G. J. and Bromberg, J. S. (2003) FTY720 stimulates multidrug transporter- and cysteinyl leukotriene-dependent T cell chemotaxis to lymph nodes. J. Clin. Invest. 111, 627-637 https://doi.org/10.1172/JCI200316200
  57. Ibrahim, F. B., Pang, S. J. and Melendez, A. J. (2004) Anaphylatoxin signaling in human neutrophils. A key role for sphingosine kinase. J. Biol. Chem. 279, 44802-44811 https://doi.org/10.1074/jbc.M403977200
  58. Igarashi, J. and Michel, T. (2001) Sphingosine 1-phosphate and isoform-specific activation of phosphoinositide 3-kinase beta. Evidence for divergence and convergence of receptor-regulated endothelial nitric-oxide synthase signaling pathways. J. Biol. Chem. 276, 36281-36288 https://doi.org/10.1074/jbc.M105628200
  59. Igarashi, J., Erwin, P. A., Dantas, A. P., Chen, H. and Michel, T. (2003) VEGF induces S1P1 receptors in endothelial cells: Implications for cross-talk between sphingolipid and growth factor receptors. Proc. Natl. Acad. Sci. USA 100, 10664-10669 https://doi.org/10.1073/pnas.1934494100
  60. Igarashi, N., Okada, T., Hayashi, S., Fujita, T., Jahangeer, S. and Nakamura, S. (2003) Sphingosine kinase 2 is a nuclear protein and inhibits DNA synthesis. J. Biol. Chem. 278, 46832-46839 https://doi.org/10.1074/jbc.M306577200
  61. Inagaki, Y., Li, P. Y., Wada, A., Mitsutake, S. and Igarashi, Y. (2003) Identification of functional nuclear export sequences in human sphingosine kinase 1. Biochem. Biophys. Res. Commun. 311, 168-173 https://doi.org/10.1016/j.bbrc.2003.09.194
  62. Johnson, K. R., Becker, K. P., Facchinetti, M. M., Hannun, Y. A. and Obeid, L. M. (2002) PKC-dependent activation of sphingosine kinase 1 and translocation to the plasma membrane. Extracellular release of sphingosine-1-phosphate induced by phorbol 12-myristate 13-acetate (PMA). J. Biol. Chem. 277, 35257-35262 https://doi.org/10.1074/jbc.M203033200
  63. Jin, Z. Q., Goetzl, E. J. and Karliner, J. S. (2004) Sphingosine kinase activation mediates ischemic preconditioning in murine heart. Circulation 110, 1980-1989 https://doi.org/10.1161/01.CIR.0000143632.06471.93
  64. Jin, Z. Q., Zhou, H. Z., Zhu, P., Honbo, N., Mochly-Rosen, D., Messing, R. O., Goetzl, E. J., Karliner, J. S. and Gray, M. O. (2002) 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. 282, H1970- 1977
  65. Jolly, P. S., Bektas, M., Olivera, A., Gonzalez-Espinosa, C., Proia, R. L., Rivera, J., Milstien, S. and Spiegel, S. (2004) Transactivation of sphingosine-1-phosphate receptors by FcepsilonRI triggering is required for normal mast cell degranulation and chemotaxis. J. Exp. Med. 199, 959-970 https://doi.org/10.1084/jem.20030680
  66. Jolly, P. S., Bektas, M., Watterson, K. R., Sankala, H., Payne, S. G., Milstien, S. and Spiegel, S. (2005) Expression of SphK1 impairs degranulation and motility of RBL-2H3 mast cells by desensitizing S1P receptors. Blood 105, 4736-4742 https://doi.org/10.1182/blood-2004-12-4686
  67. Kaneider, N. C., Lindner, J., Feistritzer, C., Sturn, D. H., Mosheimer, B. A., Djanani, A. M. and Wiedermann, C. J. (2004) The immune modulator FTY720 targets sphingosinekinase- dependent migration of human monocytes in response to amyloid beta-protein and its precursor. FASEB J. 18, 1309- 1311 https://doi.org/10.1096/fj.03-1050fje
  68. Katsuma, S., Hada, Y., Ueda, T., Shiojima, S., Hirasawa, A., Tanoue, A., Takagaki, K., Ohgi, T., Yano, J. and Tsujimoto, G. (2002) Signalling mechanisms in sphingosine 1-phosphatepromoted mesangial cell proliferation. Genes Cells 7, 1217- 1230 https://doi.org/10.1046/j.1365-2443.2002.00594.x
  69. Katsuma, S., Hada, Y., Shiojima, S., Hirasawa, A., Tanoue, A., Takagaki, K., Ohgi, T., Yano, J. and Tsujimoto, G. (2003) Transcriptional profiling of gene expression patterns during sphingosine 1-phosphate-induced mesangial cell proliferation. Biochem. Biophys. Res. Commun. 300, 577-584 https://doi.org/10.1016/S0006-291X(02)02850-4
  70. Kawamori, T., Osta, W., Johnson, K. R., Pettus, B. J., Bielawski, J., Tanaka, T., Wargovich, M. J., Reddy, B. S., Hannun, Y. A., Obeid, L. M. and Zhou, D. (2006) Sphingosine kinase 1 is upregulated in colon carcinogenesis. FASEB J. 20, 386-388 https://doi.org/10.1096/fj.05-4331fje
  71. Khan, W. A., Dobrowsky, R., el Touny, S. and Hannun, Y. A. (1990) Protein kinase C and platelet inhibition by D-erythrosphingosine: comparison with N,N-dimethylsphingosine and commercial preparation. Biochem. Biophys. Res. Commun. 172, 683-691 https://doi.org/10.1016/0006-291X(90)90728-6
  72. Kimura, T., Sato, K., Kuwabara, A., Tomura, H., Ishiwara, M., Kobayashi, I., Ui, M. and Okajima, F. (2001) Sphingosine 1- phosphate may be a major component of plasma lipoproteins responsible for the cytoprotective actions in human umbilical vein endothelial cells. J. Biol. Chem. 276, 31780-31785 https://doi.org/10.1074/jbc.M104353200
  73. Kimura, T., Sato, K., Malchinkhuu, E., Tomura, H., Tamama, K., Kuwabara, A., Murakami, M. and Okajima, F. (2003) Highdensity lipoprotein stimulates endothelial cell migration and survival through sphingosine 1-phosphate and its receptors. Arterioscler. Thromb. Vasc. Biol. 23, 1283-1288 https://doi.org/10.1161/01.ATV.0000079011.67194.5A
  74. Kleuser, B., Cuvillier, O. and Spiegel, S. (1998) 1Alpha,25- dihydroxyvitamin D3 inhibits programmed cell death in HL-60 cells by activation of sphingosine kinase. Cancer Res. 58, 1817-1824
  75. Kleuser, B., Maceyka, M., Milstien, S. and Spiegel, S. (2001) Stimulation of nuclear sphingosine kinase activity by plateletderived growth factor. FEBS Lett. 503, 85-90 https://doi.org/10.1016/S0014-5793(01)02697-7
  76. Kohama, T., Olivera, A., Edsall, L., Nagiec, M. M., Dickson, R. and Spiegel, S. (1998) Molecular cloning and functional characterization of murine sphingosine kinase. J. Biol. Chem. 273, 23722-23728 https://doi.org/10.1074/jbc.273.37.23722
  77. Kimura, T., Watanabe, T., Sato, K., Kon, J., Tomura, H., Tamama, K., Kuwabara, A., Kanda, T., Kobayashi, I., Ohta, H., Ui, M. and Okajima, F. (2000) Sphingosine 1-phosphate stimulates proliferation and migration of human endothelial cells possibly through the lipid receptors, Edg-1 and Edg-3. Biochem. J. 348, 71-76 https://doi.org/10.1042/0264-6021:3480071
  78. Kono, M., Mi, Y., Liu, Y., Sasaki, T., Allende, M. L., Wu, Y. P., Yamashita, T. and Proia, R. L. (2004) The sphingosine-1- phosphate receptors S1P1, S1P2, and S1P3 function coordinately during embryonic angiogenesis. J. Biol. Chem. 279, 29367-29373 https://doi.org/10.1074/jbc.M403937200
  79. Krump-Konvalinkova, V., Yasuda, S., Rubic, T., Makarova, N., Mages, J., Erl, W., Vosseler, C., Kirkpatrick, C. J., Tigyi, G. and Siess, W. (2005) Stable knock-down of the sphingosine 1- phosphate receptor S1P1 influences multiple functions of human endothelial cells. Arterioscler. Thromb. Vasc. Biol. 25, 546-552 https://doi.org/10.1161/01.ATV.0000154360.36106.d9
  80. Lanterman, M. M. and Saba, J. D. (1998) Characterization of sphingosine kinase (SK) activity in Saccharomyces cerevisiae and isolation of SK-deficient mutants. Biochem. J. 332, 525- 531 https://doi.org/10.1042/bj3320525
  81. Lacana, E., Maceyka, M., Milstien, S. and Spiegel, S. (2002) Cloning and characterization of a protein kinase A anchoring protein (AKAP)-related protein that interacts with and regulates sphingosine kinase 1 activity. J. Biol. Chem. 277, 32947-32953 https://doi.org/10.1074/jbc.M202841200
  82. Lee, C., Xu, D. Z., Feketeova, E., Kannan, K. B., Yun, J. K., Deitch, E. A., Fekete, Z., Livingston, D. H. and Hauser, C. J. (2004) Attenuation of shock-induced acute lung injury by sphingosine kinase inhibition. J. Trauma. 57, 955-960 https://doi.org/10.1097/01.TA.0000149495.44582.76
  83. Lee, M. J., Thangada, S., Paik, J. H., Sapkota, G. P., Ancellin, N., Chae, S. S., Wu, M., Morales-Ruiz, M., Sessa, W. C., Alessi, D. R. and Hla, T. (2001) Akt-mediated phosphorylation of the G protein-coupled receptor EDG-1 is required for endothelial cell chemotaxis. Mol. Cell 8, 693-704 https://doi.org/10.1016/S1097-2765(01)00324-0
  84. Lee, O. H., Kim, Y. M., Lee, Y. M., Moon, E. J., Lee, D. J., Kim, J. H., Kim, K. W. and Kwon, Y. G. (1999) Sphingosine 1- phosphate induces angiogenesis: its angiogenic action and signaling mechanism in human umbilical vein endothelial cells. Biochem. Biophys. Res. Commun. 264, 743-750 https://doi.org/10.1006/bbrc.1999.1586
  85. Licht, T., Tsirulnikov, L., Reuveni, H., Yarnitzky, T. and Ben- Sasson, S. A. (2003) Induction of pro-angiogenic signaling by a synthetic peptide derived from the second intracellular loop of S1P3 (EDG3). Blood 102, 2099-2107 https://doi.org/10.1182/blood-2002-12-3634
  86. Limaye, V. S., Li, X., Hahn, C., Xia, P., Berndt, M. C., Vadas, M. A. and Gamble, J. R. (2005) Sphingosine kinase-1 enhances endothelial cell survival through a PECAM-1-dependent activation of PI-3K/Akt and regulation of Bcl-2 family members. Blood 105, 3169-3177 https://doi.org/10.1182/blood-2004-02-0452
  87. Liu, H., Sugiura, M., Nava, V. E., Edsall, L. C., Kono, K., Poulton, S., Milstien, S., Kohama, T. and Spiegel, S. (2000) Molecular cloning and functional characterization of a novel mammalian sphingosine kinase type 2 isoform. J. Biol. Chem. 275, 19513-19520 https://doi.org/10.1074/jbc.M002759200
  88. Liu, H., Toman, R. E., Goparaju, S., Maceyka, M., Nava, V. E., Sankala, H., Payne, S. G., Bektas, M., Ishii, I., Chun, J., Milstien, S. and Spiegel, S. (2003) Sphingosine kinase type 2 is a putative BH3-Only protein that induces apoptosis. J. Biol. Chem.
  89. Liu, Y., Wada, R., Yamashita, T., Mi, Y., Deng, C. X., Hobson, J. P., Rosenfeldt, H. M., Nava, V. E., Chae, S. S., Lee, M. J., Liu, C. H., Hla, T., Spiegel, S. and Proia, R. L. (2000) Edg-1, the G protein-coupled receptor for sphingosine-1-phosphate, is essential for vascular maturation. J. Clin. Invest. 106, 951-961 https://doi.org/10.1172/JCI10905
  90. Louie, D. D., Kisic, A. and Schroefer, G. J. Jr. (1976) Sphingolipid base metabolism. Partial purification and properties of sphinganine kinase of brain. J. Biol. Chem. 251, 4557-4564
  91. Maceyka, M., Nava, V. E., Milstien, S. and Spiegel, S. (2004) Aminoacylase 1 is a sphingosine kinase 1-interacting protein. FEBS Lett. 568, 30-34 https://doi.org/10.1016/j.febslet.2004.04.093
  92. Maceyka, M., Payne, S. G., Milstien, S. and Spiegel, S. (2002) Sphingosine kinase, sphingosine-1-phosphate, and apoptosis. Biochim. Biophys. Acta. 1585, 193-201 https://doi.org/10.1016/S1388-1981(02)00341-4
  93. Machwate, M., Rodan, S. B., Rodan, G. A. and Harada, S. I. (1998) Sphingosine kinase mediates cyclic AMP suppression of apoptosis in rat periosteal cells. Mol. Pharmacol. 54, 70-77 https://doi.org/10.1124/mol.54.1.70
  94. Malik, Z. A., Thompson, C. R., Hashimi, S., Porter, B., Iyer, S. S. and Kusner, D. J. (2003) Cutting edge: Mycobacterium tuberculosis blocks $Ca^{2+}$ signaling and phagosome maturation in human macrophages via specific inhibition of sphingosine kinase. J. Immunol. 170, 2811-2815 https://doi.org/10.4049/jimmunol.170.6.2811
  95. Mandala, S., Hajdu, R., Bergstrom, J., Quackenbush, E., Xie, J., Milligan, J., Thornton, R., Shei, G. J., Card, D., Keohane, C., Rosenbach, M., Hale, J., Lynch, C. L., Rupprecht, K., Parsons, W. and Rosen, H. (2002) Alteration of lymphocyte trafficking by sphingosine-1-phosphate receptor agonists. Science 296, 346-349 https://doi.org/10.1126/science.1070238
  96. Mao, C., Saba, J. D. and Obeid, L. M. (1999) The dihydrosphingosine- 1-phosphate phosphatases of Saccharomyces cerevisiae are important regulators of cell proliferation and heat stress responses. Biochem. J. 342, 667-675 https://doi.org/10.1042/0264-6021:3420667
  97. Matloubian, M., Lo, C. G., Cinamon, G., Lesneski, M. J., Xu, Y., Brinkmann, V., Allende, M. L., Proia, R. L. and Cyster, J. G. (2004) Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1. Nature 427, 355-360 https://doi.org/10.1038/nature02284
  98. Matsushita, K., Morrell, C. N. and Lowenstein, C. J. (2004) Sphingosine 1-phosphate activates Weibel-Palade body exocytosis. Proc. Natl. Acad. Sci. USA 101, 11483-11487 https://doi.org/10.1073/pnas.0400185101
  99. Mazurek, N., Megidish, T., Hakomori, S. and Igarashi, Y. (1994) Regulatory effect of phorbol esters on sphingosine kinase in BALB/C 3T3 fibroblasts (variant A31): demonstration of cell type-specific response--a preliminary note. Biochem. Biophys. Res. Commun. 198, 1-9 https://doi.org/10.1006/bbrc.1994.1001
  100. Melendez, A., Floto, R. A., Cameron, A. J., Gillooly, D. J., Harnett, M. M. and Allen, J. M. (1998) A molecular switch changes the signalling pathway used by the Fc gamma RI antibody receptor to mobilise calcium. Curr. Biol. 8, 210-221 https://doi.org/10.1016/S0960-9822(98)70085-5
  101. Melendez, A. J., Carlos-Dias, E., Gosink, M., Allen, J. M. and Takacs, L. (2000) Human sphingosine kinase: molecular cloning, functional characterization and tissue distribution. Gene 251, 19-26 https://doi.org/10.1016/S0378-1119(00)00205-5
  102. Melendez, A. J. and Khaw, A. K. (2002) Dichotomy of $Ca^{2+}$ signals triggered by different phospholipid pathways in antigen stimulation of human mast cells. J. Biol. Chem. 277, 17255- 17262 https://doi.org/10.1074/jbc.M110944200
  103. Melendez, A. J. and Ibrahim, F. B. (2004) Antisense knockdown of sphingosine kinase 1 in human macrophages inhibits C5a receptor-dependent signal transduction, $Ca^{2+}$ signals, enzyme release, cytokine production, and chemotaxis. J. Immunol. 173, 1596-1603 https://doi.org/10.4049/jimmunol.173.3.1596
  104. Melendez, A., Floto, R. A., Gillooly, D. J., Harnett, M. M. and Allen, J. M. (1998) FcgammaRI coupling to phospholipase D initiates sphingosine kinase-mediated calcium mobilization and vesicular trafficking. J. Biol. Chem. 273, 9393-9402 https://doi.org/10.1074/jbc.273.16.9393
  105. Meyer Zu Heringdorf, D. (2004) Lysophospholipid receptordependent and -independent calcium signaling. J. Cell. Biochem. 92, 937-948 https://doi.org/10.1002/jcb.20107
  106. Meyer zu Heringdorf, D., Lass, H., Alemany, R., Laser, K. T., Neumann, E., Zhang, C., Schmidt, M., Rauen, U., Jakobs, K. H. and van Koppen, C. J. (1998) Sphingosine kinase-mediated $Ca^{2+}$ signalling by G-protein-coupled receptors. EMBO J. 17, 2830-2837 https://doi.org/10.1093/emboj/17.10.2830
  107. Meyer zu Heringdorf, D., Liliom, K., Schaefer, M., Danneberg, K., Jaggar, J. H., Tigyi, G., and Jakobs, K. H. (2003) Photolysis of intracellular caged sphingosine-1-phosphate causes $Ca^{2+}$ mobilization independently of G-protein-coupled receptors. FEBS Lett. 554, 443-449 https://doi.org/10.1016/S0014-5793(03)01219-5
  108. Meyer zu Heringdorf, D., Lass, H., Kuchar, I., Alemany, R., Guo, Y., Schmidt, M. and Jakobs, K. H. (1999) Role of sphingosine kinase in $Ca^{2+}$ signalling by epidermal growth factor receptor. FEBS Lett. 461, 217-222 https://doi.org/10.1016/S0014-5793(99)01463-5
  109. Min, J., Traynor, D., Stegner, A. L., Zhang, L., Hanigan, M. H., Alexander, H. and Alexander, S. (2005) Sphingosine kinase regulates the sensitivity of Dictyostelium discoideum cells to the anticancer drug cisplatin. Eukaryot. Cell 4, 178-189 https://doi.org/10.1128/EC.4.1.178-189.2005
  110. Miura, Y., Yatomi, Y., Rile, G., Ohmori, T., Satoh, K. and Ozaki, Y. (2000) Rho-mediated phosphorylation of focal adhesion kinase and myosin light chain in human endothelial cells stimulated with sphingosine 1-phosphate, a bioactive lysophospholipid released from activated platelets. J. Biochem. (Tokyo) 127, 909-914 https://doi.org/10.1093/oxfordjournals.jbchem.a022686
  111. Nagiec, M. M., Skrzypek, M., Nagiec, E. E., Lester, R. L. and Dickson, R. C. (1998) The LCB4 (YOR171c) and LCB5 (YLR260w) genes of Saccharomyces encode sphingoid long chain base kinases. J. Biol. Chem. 273, 19437-19442 https://doi.org/10.1074/jbc.273.31.19437
  112. Nakade, Y., Banno, Y., K, T. K., Hagiwara, K., Sobue, S., Koda, M., Suzuki, M., Kojima, T., Takagi, A., Asano, H., Nozawa, Y. and Murate, T. (2003) Regulation of sphingosine kinase 1 gene expression by protein kinase C in a human leukemia cell line, MEG-O1. Biochim. Biophys. Acta. 1635, 104-116 https://doi.org/10.1016/j.bbalip.2003.11.001
  113. Nava, V. E., Cuvillier, O., Edsall, L. C., Kimura, K., Milstien, S., Gelmann, E. P. and Spiegel, S. (2000) Sphingosine enhances apoptosis of radiation-resistant prostate cancer cells. Cancer Res. 60, 4468-4474
  114. Nava, V. E., Hobson, J. P., Murthy, S., Milstien, S. and Spiegel, S. (2002) Sphingosine kinase type 1 promotes estrogen-dependent tumorigenesis of breast cancer MCF-7 cells. Exp. Cell Res. 281, 115-127 https://doi.org/10.1006/excr.2002.5658
  115. Nava, V. E., Lacana, E., Poulton, S., Liu, H., Sugiura, M., Kono, K., Milstien, S., Kohama, T. and Spiegel, S. (2000) Functional characterization of human sphingosine kinase-1. FEBS Lett. 473, 81-84 https://doi.org/10.1016/S0014-5793(00)01510-6
  116. Ng, C. K., Carr, K., McAinsh, M. R., Powell, B. and Hetherington, A. M. (2001) Drought-induced guard cell signal transduction involves sphingosine-1-phosphate. Nature 410, 596-599 https://doi.org/10.1038/35069092
  117. Nishiura, H., Tamura, K., Morimoto, Y. and Imai, H. (2000) Characterization of sphingolipid long-chain base kinase in Arabidopsis thaliana. Biochem. Soc. Trans. 28, 747-748 https://doi.org/10.1042/BST0280747
  118. Nofer, J. R., Levkau, B., Wolinska, I., Junker, R., Fobker, M., von Eckardstein, A., Seedorf, U. and Assmann, G. (2001) Suppression of endothelial cell apoptosis by high density lipoproteins (HDL) and HDL-associated lysosphingolipids. J. Biol. Chem. 276, 34480-34485 https://doi.org/10.1074/jbc.M103782200
  119. Nofer, J. R., van der Giet, M., Tolle, M., Wolinska, I., von Wnuck Lipinski, K., Baba, H. A., Tietge, U. J., Godecke, A., Ishii, I., Kleuser, B., Schafers, M., Fobker, M., Zidek, W., Assmann, G., Chun, J. and Levkau, B. (2004) HDL induces NO-dependent vasorelaxation via the lysophospholipid receptor S1P3. J. Clin. Invest. 113, 569-581 https://doi.org/10.1172/JCI200418004
  120. Olivera, A., Edsall, L., Poulton, S., Kazlauskas, A. and Spiegel, S. (1999) Platelet-derived growth factor-induced activation of sphingosine kinase requires phosphorylation of the PDGF receptor tyrosine residue responsible for binding of PLCgamma. FASEB J. 13, 1593-1600 https://doi.org/10.1096/fasebj.13.12.1593
  121. Olivera, A., Kohama, T., Tu, Z., Milstien, S. and Spiegel, S. (1998) Purification and characterization of rat kidney sphingosine kinase. J. Biol. Chem. 273, 12576-12583 https://doi.org/10.1074/jbc.273.20.12576
  122. Olivera, A., Rosenthal, J. and Spiegel, S. (1996) Effect of acidic phospholipids on sphingosine kinase. J. Cell. Biochem. 60, 529-537 https://doi.org/10.1002/(SICI)1097-4644(19960315)60:4<529::AID-JCB9>3.0.CO;2-U
  123. Olivera, A. and Spiegel, S. (1993) Sphingosine-1-phosphate as second messenger in cell proliferation induced by PDGF and FCS mitogens. Nature 365, 557-560 https://doi.org/10.1038/365557a0
  124. Olivera, A. and Spiegel, S. (2001) Sphingosine kinase: a mediator of vital cellular functions. Prostaglandins 64, 123-134 https://doi.org/10.1016/S0090-6980(01)00108-3
  125. Olivera, A., Kohama, T., Edsall, L., Nava, V., Cuvillier, O., Poulton, S. and Spiegel, S. (1999) Sphingosine kinase expression increases intracellular sphingosine-1-phosphate and promotes cell growth and survival. J. Cell Biol. 147, 545-558 https://doi.org/10.1083/jcb.147.3.545
  126. Olivera, A., Rosenfeldt, H. M., Bektas, M., Wang, F., Ishii, I., Chun, J., Milstien, S. and Spiegel, S. (2003) 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. 278, 46452-46460 https://doi.org/10.1074/jbc.M308749200
  127. Okoshi, H., Hakomori, S., Nisar, M., Zhou, Q. H., Kimura, S., Tashiro, K. and Igarashi, Y. (1991) Cell membrane signaling as target in cancer therapy. II: Inhibitory effect of N,N,Ntrimethylsphingosine on metastatic potential of murine B16 melanoma cell line through blocking of tumor cell-dependent platelet aggregation. Cancer Res. 51, 6019-6024
  128. Paik, J. H., Skoura, A., Chae, S. S., Cowan, A. E., Han, D. K., Proia, R. L. and Hla, T. (2004) Sphingosine 1-phosphate receptor regulation of N-cadherin mediates vascular stabilization. Genes Dev. 18, 2392-2403 https://doi.org/10.1101/gad.1227804
  129. Park, Y. S., Hakomori, S., Kawa, S., Ruan, F. and Igarashi, Y. (1994) Liposomal N,N,N-trimethylsphingosine (TMS) as an inhibitor of B16 melanoma cell growth and metastasis with reduced toxicity and enhanced drug efficacy compared to free TMS: cell membrane signaling as a target in cancer therapy III. Cancer Res. 54, 2213-2217
  130. Peng, X., Hassoun, P. M., Sammani, S., McVerry, B. J., Burne, M. J., Rabb, H., Pearse, D., Tuder, R. M. and Garcia, J. G. (2004) Protective effects of sphingosine 1-phosphate in murine endotoxin-induced inflammatory lung injury. Am. J. Respir. Crit. Care Med. 169, 1245-1251 https://doi.org/10.1164/rccm.200309-1258OC
  131. Pettus, B. J., Bielawski, J., Porcelli, A. M., Reames, D. L., Johnson, K. R., Morrow, J., Chalfant, C. E., Obeid, L. M. and Hannun, Y. A. (2003) The sphingosine kinase 1/sphingosine-1- phosphate pathway mediates COX-2 induction and PGE2 production in response to TNF-alpha. FASEB J. 17, 1411-1421 https://doi.org/10.1096/fj.02-1038com
  132. Pettus, B. J., Kitatani, K., Chalfant, C. E., Taha, T. A., Kawamori, T., Bielawski, J., Obeid, L. M. and Hannun, Y. A. (2005) The coordination of prostaglandin E2 production by sphingosine-1- phosphate and ceramide-1-phosphate. Mol. Pharmacol. 68, 330-335
  133. Pinschewer, D. D., Ochsenbein, A. F., Odermatt, B., Brinkmann, V., Hengartner, H. and Zinkernagel, R. M. (2000) FTY720 immunosuppression impairs effector T cell peripheral homing without affecting induction, expansion, and memory. J. Immunol. 164, 5761-5770 https://doi.org/10.4049/jimmunol.164.11.5761
  134. Pitson, S. M., D'Andrea R, J., Vandeleur, L., Moretti, P. A., Xia, P., Gamble, J. R., Vadas, M. A. and Wattenberg, B. W. (2000) Human sphingosine kinase: purification, molecular cloning and characterization of the native and recombinant enzymes. Biochem. J. 350, 429-441 https://doi.org/10.1042/0264-6021:3500429
  135. Pitson, S. M., Moretti, P. A., Zebol, J. R., Lynn, H. E., Xia, P., Vadas, M. A. and Wattenberg, B. W. (2003) Activation of sphingosine kinase 1 by ERK1/2-mediated phosphorylation. EMBO J. 22, 5491-5500 https://doi.org/10.1093/emboj/cdg540
  136. Pitson, S. M., Moretti, P. A., Zebol, J. R., Zareie, R., Derian, C. K., Darrow, A. L., Qi, J., D'Andrea, R. J., Bagley, C. J., Vadas, M. A. and Wattenberg, B. W. (2002) The nucleotidebinding site of human sphingosine kinase 1. J. Biol. Chem. 277, 49545-49553 https://doi.org/10.1074/jbc.M206687200
  137. Pitson, S. M., Moretti, P. A., Zebol, J. R., Xia, P., Gamble, J. R., Vadas, M. A., D'Andrea, R. J. and Wattenberg, B. W. (2000) Expression of a catalytically inactive sphingosine kinase mutant blocks agonist-induced sphingosine kinase activation. A dominant-negative sphingosine kinase. J. Biol. Chem. 275, 33945-33950 https://doi.org/10.1074/jbc.M006176200
  138. Pitson, S. M., Xia, P., Leclercq, T. M., Moretti, P. A., Zebol, J. R., Lynn, H. E., Wattenberg, B. W. and Vadas, M. A. (2005) Phosphorylation-dependent translocation of sphingosine kinase to the plasma membrane drives its oncogenic signalling. J. Exp. Med. 201, 49-54 https://doi.org/10.1084/jem.20040559
  139. Rhoads, A. R. and Friedberg, F. (1997) Sequence motifs for calmodulin recognition. FASEB J. 11, 331-340 https://doi.org/10.1096/fasebj.11.5.9141499
  140. Ren, R., Mayer, B. J., Cicchetti, P. and Baltimore, D. (1993) Identification of a ten-amino acid proline-rich SH3 binding site. Science 259, 1157-1161 https://doi.org/10.1126/science.8438166
  141. Rosenfeldt, H. M., Hobson, J. P., Milstien, S. and Spiegel, S. (2001) The sphingosine-1-phosphate receptor EDG-1 is essential for platelet-derived growth factor-induced cell motility. Biochem. Soc. Trans. 29, 836-839 https://doi.org/10.1042/BST0290836
  142. Rikitake, Y., Hirata, K., Kawashima, S., Ozaki, M., Takahashi, T., Ogawa, W., Inoue, N. and Yokoyama, M. (2002) Involvement of endothelial nitric oxide in sphingosine-1-phosphate-induced angiogenesis. Arterioscler. Thromb Vasc. Biol. 22, 108-114 https://doi.org/10.1161/hq0102.101843
  143. Rius, R. A., Edsall, L. C. and Spiegel, S. (1997) Activation of sphingosine kinase in pheochromocytoma PC12 neuronal cells in response to trophic factors. FEBS Lett. 417, 173-176 https://doi.org/10.1016/S0014-5793(97)01277-5
  144. Rosen, H., Sanna, G. and Alfonso, C. (2003) Egress: a receptorregulated step in lymphocyte trafficking. Immunol. Rev. 195, 160-177 https://doi.org/10.1034/j.1600-065X.2003.00068.x
  145. Roviezzo, F., Del Galdo, F., Abbate, G., Bucci, M., D'Agostino, B., Antunes, E., De Dominicis, G., Parente, L., Rossi, F., Cirino, G. and De Palma, R. (2004) Human eosinophil chemotaxis and selective in vivo recruitment by sphingosine 1- phosphate. Proc. Natl. Acad. Sci. USA 101, 11170-11175 https://doi.org/10.1073/pnas.0401439101
  146. Safadi-Chamberlain, F., Wang, L. P., Payne, S. G., Lim, C. U., Stratford, S., Chavez, J. A., Fox, M. H., Spiegel, S. and Summers, S. A. (2005) Effect of a membrane-targeted sphingosine kinase 1 on cell proliferation and survival. Biochem. J. 388, 827-834 https://doi.org/10.1042/BJ20041726
  147. Sanchez, T., Estrada-Hernandez, T., Paik, J. H., Wu, M. T., Venkataraman, K., Brinkmann, V., Claffey, K. and Hla, T. (2003) Phosphorylation and action of the immunomodulator FTY720 inhibits vascular endothelial cell growth factor-induced vascular permeability. J. Biol. Chem. 278, 47281-47290 https://doi.org/10.1074/jbc.M306896200
  148. Sanna, M. G., Liao, J., Jo, E., Alfonso, C., Ahn, M. Y., Peterson, M. S., Webb, B., Lefebvre, S., Chun, J., Gray, N. and Rosen, H. (2004) Sphingosine 1-phosphate (S1P) receptor subtypes S1P1 and S1P3, respectively, regulate lymphocyte recirculation and heart rate. J. Biol. Chem. 279, 13839-13848 https://doi.org/10.1074/jbc.M311743200
  149. Schaphorst, K. L., Chiang, E., Jacobs, K. N., Zaiman, A., Natarajan, V., Wigley, F. and Garcia, J. G. (2003) Role of sphingosine-1 phosphate in the enhancement of endothelial barrier integrity by platelet-released products. Am. J. Physiol. Lung Cell Mol. Physiol. 285, L258-267
  150. Shu, X., Wu, W., Mosteller, R. D. and Broek, D. (2002) Sphingosine kinase mediates vascular endothelial growth factor-induced activation of ras and mitogen-activated protein kinases. Mol. Cell. Biol. 22, 7758-7768 https://doi.org/10.1128/MCB.22.22.7758-7768.2002
  151. Spiegel, S. and Milstien, S. (2003) Sphingosine-1-phosphate: an enigmatic signalling lipid. Nat. Rev. Mol. Cell Biol. 4, 397-407 https://doi.org/10.1038/nrm1103
  152. Stahelin, R. V., Hwang, J. H., Kim, J. H., Park, Z. Y., Johnson, K. R., Obeid, L. M. and Cho, W. (2005) The mechanism of membrane targeting of human sphingosine kinase 1. J. Biol. Chem. 280, 43030-43038 https://doi.org/10.1074/jbc.M507574200
  153. Stoffel, W., Hellenbroich, B. and Heimann, G. (1973) Properties and specificities of sphingosine kinase from blood platelets. Hoppe. Seylers. Z. Physiol. Chem. 354, 1311-1316 https://doi.org/10.1515/bchm2.1973.354.2.1311
  154. Stoffel, W., Heimann, G. and Hellenbroich, B. (1973) Sphingosine kinase in blood platelets. Hoppe. Seylers. Z. Physiol. Chem. 354, 562-566 https://doi.org/10.1515/bchm2.1973.354.1.562
  155. Sugiura, M., Kono, K., Liu, H., Shimizugawa, T., Minekura, H., Spiegel, S. and Kohama, T. (2002) Ceramide kinase, a novel lipid kinase. Molecular cloning and functional characterization. J. Biol. Chem. 277, 23294-23300 https://doi.org/10.1074/jbc.M201535200
  156. Sukocheva, O. A., Wang, L., Albanese, N., Pitson, S. M., Vadas, M. A. and Xia, P. (2003) Sphingosine kinase transmits estrogen signaling in human breast cancer cells. Mol. Endocrinol. 17, 2002-2012 https://doi.org/10.1210/me.2003-0119
  157. Smith, R. E., Patel, V., Seatter, S. D., Deehan, M. R., Brown, M. H., Brooke, G. P., Goodridge, H. S., Howard, C. J., Rigley, K. P., Harnett, W. and Harnett, M. M. (2003) A novel MyD-1 (SIRP-1alpha) signaling pathway that inhibits LPS-induced TNFalpha production by monocytes. Blood 102, 2532-2540 https://doi.org/10.1182/blood-2002-11-3596
  158. Spiegel, S. (1999) Sphingosine 1-phosphate: a prototype of a new class of second messengers. J. Leukoc. Biol. 65, 341-344 https://doi.org/10.1002/jlb.65.3.341
  159. Taha, T. A., Kitatani, K., Bielawski, J., Cho, W., Hannun, Y. A. and Obeid, L. M. (2005) Tumor necrosis factor induces the loss of sphingosine kinase-1 by a cathepsin B-dependent mechanism. J. Biol. Chem. 280, 17196-17202 https://doi.org/10.1074/jbc.M413744200
  160. Taha, T. A., Osta, W., Kozhaya, L., Bielawski, J., Johnson, K. R., Gillanders, W. E., Dbaibo, G. S., Hannun, Y. A. and Obeid, L. M. (2004) Down-regulation of sphingosine kinase-1 by DNA damage: dependence on proteases and p53. J. Biol. Chem. 279, 20546-20554 https://doi.org/10.1074/jbc.M401259200
  161. Tanimoto, T., Jin, Z. G. and Berk, B. C. (2002) Transactivation of vascular endothelial growth factor (VEGF) receptor Flk-1/KDR is involved in sphingosine 1-phosphate-stimulated phosphorylation of Akt and endothelial nitric-oxide synthase (eNOS). J. Biol. Chem. 277, 42997-43001 https://doi.org/10.1074/jbc.M204764200
  162. Thompson, C. R., Iyer, S. S., Melrose, N., Vanoosten, R., Johnson, K., Pitson, S. M., Obeid, L. M. and Kusner, D. J. (2005) Sphingosine kinase 1 (SK1) is recruited to nascent phagosomes in human macrophages: Inhibition of SK1 translocation by mycobacterium tuberculosis. J. Immunol. 174, 3551-3561 https://doi.org/10.4049/jimmunol.174.6.3551
  163. Tolle, M., Levkau, B., Keul, P., Brinkmann, V., Giebing, G., Schonfelder, G., Schafers, M., von Wnuck Lipinski, K., Jankowski, J., Jankowski, V., Chun, J., Zidek, W. and van der Giet, M. (2005) Immunomodulator FTY720 induces eNOS-dependent arterial vasodilatation via the lysophospholipid receptor S1P3. Circ. Res. 96, 913-920 https://doi.org/10.1161/01.RES.0000164321.91452.00
  164. Toman, R. E., Payne, S. G., Watterson, K. R., Maceyka, M., Lee, N. H., Milstien, S., Bigbee, J. W. and Spiegel, S. (2004) Differential transactivation of sphingosine-1-phosphate receptors modulates NGF-induced neurite extension. J. Cell Biol. 166, 381-392 https://doi.org/10.1083/jcb.200402016
  165. Urtz, N., Olivera, A., Bofill-Cardona, E., Csonga, R., Billich, A., Mechtcheriakova, D., Bornancin, F., Woisetschlager, M., Rivera, J. and Baumruker, T. (2004) Early activation of sphingosine kinase in mast cells and recruitment to FcepsilonRI are mediated by its interaction with Lyn kinase. Mol. Cell. Biol. 24, 8765-8777 https://doi.org/10.1128/MCB.24.19.8765-8777.2004
  166. Van Brocklyn, J. R., Lee, M. J., Menzeleev, R., Olivera, A., Edsall, L., Cuvillier, O., Thomas, D. M., Coopman, P. J., Thangada, S., Liu, C. H., Hla, T. and Spiegel, S. (1998) Dual actions of sphingosine-1-phosphate: extracellular through the Gi-coupled receptor Edg-1 and intracellular to regulate proliferation and survival. J. Cell Biol. 142, 229-240 https://doi.org/10.1083/jcb.142.1.229
  167. Van Brocklyn, J. R., Tu, Z., Edsall, L. C., Schmidt, R. R. and Spiegel, S. (1999) Sphingosine 1-phosphate-induced cell rounding and neurite retraction are mediated by the G proteincoupled receptor H218. J. Biol. Chem. 274, 4626-4632 https://doi.org/10.1074/jbc.274.8.4626
  168. van Koppen, C. J., Meyer zu Heringdorf, D., Alemany, R. and Jakobs, K. H. (2001) Sphingosine kinase-mediated calcium signaling by muscarinic acetylcholine receptors. Life Sci. 68, 2535-2540 https://doi.org/10.1016/S0024-3205(01)01049-9
  169. Wang, F., Van Brocklyn, J. R., Edsall, L., Nava, V. E. and Spiegel, S. (1999) Sphingosine-1-phosphate inhibits motility of human breast cancer cells independently of cell surface receptors. Cancer Res. 59, 6185-6191
  170. Wu, W., Shu, X., Hovsepyan, H., Mosteller, R. D. and Broek, D. (2003) VEGF receptor expression and signaling in human bladder tumors. Oncogene 22, 3361-3370 https://doi.org/10.1038/sj.onc.1206285
  171. Wu, W., Mosteller, R. D. and Broek, D. (2004) Sphingosine kinase protects lipopolysaccharide-activated macrophages from apoptosis. Mol. Cell. Biol. 24, 7359-7369 https://doi.org/10.1128/MCB.24.17.7359-7369.2004
  172. Xia, P., Wang, L., Moretti, P. A., Albanese, N., Chai, F., Pitson, S. M., D'Andrea, R. J., Gamble, J. R. and Vadas, M. A. (2002) Sphingosine kinase interacts with TRAF2 and dissects tumor necrosis factor-alpha signaling. J. Biol. Chem. 277, 7996-8003 https://doi.org/10.1074/jbc.M111423200
  173. Xia, P., Gamble, J. R., Rye, K. A., Wang, L., Hii, C. S., Cockerill, P., Khew-Goodall, Y., Bert, A. G., Barter, P. J. and Vadas, M. A. (1998) Tumor necrosis factor-alpha induces adhesion molecule expression through the sphingosine kinase pathway. Proc. Natl. Acad. Sci. USA 95, 14196-14201 https://doi.org/10.1073/pnas.95.24.14196
  174. Xia, P., Gamble, J. R., Wang, L., Pitson, S. M., Moretti, P. A., Wattenberg, B. W., D'Andrea, R. J. and Vadas, M. A. (2000) An oncogenic role of sphingosine kinase. Curr. Biol. 10, 1527- 1530 https://doi.org/10.1016/S0960-9822(00)00834-4
  175. Xia, P., Vadas, M. A., Rye, K. A., Barter, P. J. and Gamble, J. R. (1999) High density lipoproteins (HDL) interrupt the sphingosine kinase signaling pathway. A possible mechanism for protection against atherosclerosis by HDL. J. Biol. Chem. 274, 33143-33147 https://doi.org/10.1074/jbc.274.46.33143
  176. Xia, P., Wang, L., Gamble, J. R. and Vadas, M. A. (1999) Activation of sphingosine kinase by tumor necrosis factor-alpha inhibits apoptosis in human endothelial cells. J. Biol. Chem. 274, 34499-34505 https://doi.org/10.1074/jbc.274.48.34499
  177. Xie, J. H., Nomura, N., Koprak, S. L., Quackenbush, E. J., Forrest, M. J. and Rosen, H. (2003) Sphingosine-1-phosphate receptor agonism impairs the efficiency of the local immune response by altering trafficking of naive and antigen-activated $CD^{4+}$ T cells. J. Immunol. 170, 3662-3670 https://doi.org/10.4049/jimmunol.170.7.3662
  178. Xu, C. B., Hansen-Schwartz, J. and Edvinsson, L. (2004) Sphingosine signaling and atherogenesis. Acta. Pharmacol. Sin. 25, 849-854
  179. Xu, C. B., Zhang, Y., Stenman, E. and Edvinsson, L. (2002) D-erythro- N,N-dimethylsphingosine inhibits bFGF-induced proliferation of cerebral, aortic and coronary smooth muscle cells. Atherosclerosis 164, 237-243 https://doi.org/10.1016/S0021-9150(02)00100-4
  180. Yamanaka, M., Shegogue, D., Pei, H., Bu, S., Bielawska, A., Bielawski, J., Pettus, B., Hannun, Y. A., Obeid, L. and Trojanowska, M. (2004) Sphingosine kinase 1 (SPHK1) is induced by transforming growth factor-beta and mediates TIMP-1 up-regulation. J. Biol. Chem. 279, 53994-54001 https://doi.org/10.1074/jbc.M410144200
  181. Yatomi, Y., Igarashi, Y., Yang, L., Hisano, N., Qi, R., Asazuma, N., Satoh, K., Ozaki, Y. and Kume, S. (1997) Sphingosine 1- phosphate, a bioactive sphingolipid abundantly stored in platelets, is a normal constituent of human plasma and serum. J. Biochem. (Tokyo) 121, 969-973 https://doi.org/10.1093/oxfordjournals.jbchem.a021681
  182. Yatomi, Y., Ruan, F., Megidish, T., Toyokuni, T., Hakomori, S. and Igarashi, Y. (1996) N,N-dimethylsphingosine inhibition of sphingosine kinase and sphingosine 1-phosphate activity in human platelets. Biochemistry 35, 626-633 https://doi.org/10.1021/bi9515533
  183. Yokota, S., Taniguchi, Y., Kihara, A., Mitsutake, S. and Igarashi, Y. (2004) Asp177 in C4 domain of mouse sphingosine kinase 1a is important for the sphingosine recognition. FEBS Lett. 578, 106-110 https://doi.org/10.1016/j.febslet.2004.10.081
  184. Young, K. W., Channing, D. R. and Nahorski, S. R. (2000) Effect of dimethylsphingosine on muscarinic M(3) receptor signalling in SH-SY5Y cells. Eur. J. Pharmacol. 402, 55-59 https://doi.org/10.1016/S0014-2999(00)00509-4
  185. Young, K. W., Willets, J. M., Parkinson, M. J., Bartlett, P., Spiegel, S., Nahorski, S. R. and Challiss, R. A. (2003) $Ca^{(2+)}$/ calmodulin-dependent translocation of sphingosine kinase: role in plasma membrane relocation but not activation. Cell Calcium. 33, 119-128 https://doi.org/10.1016/S0143-4160(02)00205-1
  186. Yu, H., Chen, J. K., Feng, S., Dalgarno, D. C., Brauer, A. W. and Schreiber, S. L. (1994) Structural basis for the binding of proline-rich peptides to SH3 domains. Cell 76, 933-945 https://doi.org/10.1016/0092-8674(94)90367-0
  187. Yang, L., Yatomi, Y., Satoh, K., Igarashi, Y. and Ozaki, Y. (1999) Sphingosine 1-phosphate formation and intracellular $Ca^{2+}$ mobilization in human platelets: evaluation with sphingosine kinase inhibitors. J. Biochem. (Tokyo) 126, 84-89 https://doi.org/10.1093/oxfordjournals.jbchem.a022440
  188. Yatomi, Y., Ruan, F., Hakomori, S. and Igarashi, Y. (1995) Sphingosine-1-phosphate: a platelet-activating sphingolipid released from agonist-stimulated human platelets. Blood 86, 193-202
  189. Yatomi, Y., Yamamura, S., Ruan, F. and Igarashi, Y. (1997) Sphingosine 1-phosphate induces platelet activation through an extracellular action and shares a platelet surface receptor with lysophosphatidic acid. J. Biol. Chem. 272, 5291-5297 https://doi.org/10.1074/jbc.272.8.5291
  190. Yagi, H., Kamba, R., Chiba, K., Soga, H., Yaguchi, K., Nakamura, M. and Itoh, T. (2000) Immunosuppressant FTY720 inhibits thymocyte emigration. Eur. J. Immunol. 30, 1435-1444 https://doi.org/10.1002/(SICI)1521-4141(200005)30:5<1435::AID-IMMU1435>3.0.CO;2-O
  191. Yopp, A. C., Fu, S., Honig, S. M., Randolph, G. J., Ding, Y., Krieger, N. R. and Bromberg, J. S. (2004) FTY720-enhanced T cell homing is dependent on CCR2, CCR5, CCR7, and CXCR4: evidence for distinct chemokine compartments. J. Immunol. 173, 855-865 https://doi.org/10.4049/jimmunol.173.2.855
  192. Zhang, H., Desai, N. N., Olivera, A., Seki, T., Brooker, G. and Spiegel, S. (1991) Sphingosine-1-phosphate, a novel lipid, involved in cellular proliferation. J. Cell Biol. 114, 155-167 https://doi.org/10.1083/jcb.114.1.155

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  80. Sphingolipids in apoptosis, survival and regeneration in the nervous system vol.1758, pp.12, 2006, https://doi.org/10.1016/j.bbamem.2006.09.018
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  82. High-density lipoprotein, sphingosine 1-phosphate, and atherosclerosis vol.2, pp.1, 2008, https://doi.org/10.1016/j.jacl.2007.11.002
  83. Sphingolipids and cell death vol.12, pp.5, 2007, https://doi.org/10.1007/s10495-007-0721-0
  84. Involvement of sphingosine kinase in plant cell signalling vol.56, pp.1, 2008, https://doi.org/10.1111/j.1365-313X.2008.03579.x
  85. Simultaneous quantitation of sphingoid bases and their phosphates in biological samples by liquid chromatography/electrospray ionization tandem mass spectrometry vol.403, pp.7, 2012, https://doi.org/10.1007/s00216-012-6004-9
  86. Sphingosine-1-phosphate metabolism: A structural perspective vol.50, pp.4, 2015, https://doi.org/10.3109/10409238.2015.1039115
  87. Targeting sphingosine-1-phosphate for cancer therapy vol.95, pp.9, 2006, https://doi.org/10.1038/sj.bjc.6603400
  88. The roles of bioactive sphingolipids in resveratrol-induced apoptosis in HL60 acute myeloid leukemia cells vol.137, pp.2, 2011, https://doi.org/10.1007/s00432-010-0884-x
  89. Regulation of Ceramide Biosynthesis by TOR Complex 2 vol.7, pp.2, 2008, https://doi.org/10.1016/j.cmet.2007.11.015
  90. Modulation of cellular S1P levels with a novel, potent and specific inhibitor of sphingosine kinase-1 vol.444, pp.1, 2012, https://doi.org/10.1042/BJ20111929
  91. Renal mesangial cells: moving on sphingosine kinase-1 vol.150, pp.3, 2007, https://doi.org/10.1038/sj.bjp.0706986
  92. Efficacy of a novel sphingosine kinase inhibitor in experimental Crohn’s disease vol.18, pp.2, 2010, https://doi.org/10.1007/s10787-010-0032-x
  93. Sphingosine Kinase 1 Is Regulated by Peroxisome Proliferator-activated Receptor α in Response to Free Fatty Acids and Is Essential for Skeletal Muscle Interleukin-6 Production and Signaling in Diet-induced Obesity vol.288, pp.31, 2013, https://doi.org/10.1074/jbc.M113.477786
  94. A Sphingosine Kinase-1 Inhibitor, SKI-II, Induces Growth Inhibition and Apoptosis in Human Gastric Cancer Cells vol.15, pp.23, 2015, https://doi.org/10.7314/APJCP.2014.15.23.10381
  95. Sphingosine kinase 1 expression is regulated by signaling through PI3K, AKT2, and mTOR in human coronary artery smooth muscle cells vol.1769, pp.4, 2007, https://doi.org/10.1016/j.bbaexp.2007.03.005
  96. Sphingosine kinase 1 participates in insulin signalling and regulates glucose metabolism and homeostasis in KK/Ay diabetic mice vol.50, pp.4, 2007, https://doi.org/10.1007/s00125-006-0589-5
  97. Lactosylceramide: a lipid second messenger in neuroinflammatory disease vol.103, pp.s1, 2007, https://doi.org/10.1111/j.1471-4159.2007.04822.x
  98. Roles, regulation and inhibitors of sphingosine kinase 2 vol.280, pp.21, 2013, https://doi.org/10.1111/febs.12314
  99. K6PC-5, a novel sphingosine kinase activator, improves long-term ultraviolet light-exposed aged murine skin vol.17, pp.10, 2008, https://doi.org/10.1111/j.1600-0625.2008.00708.x
  100. Unraveling the complexities of sphingosine-1-phosphate function: The mast cell model vol.86, pp.1-4, 2008, https://doi.org/10.1016/j.prostaglandins.2008.02.005
  101. Ceramides modulate cell-surface acetylcholine receptor levels vol.1778, pp.4, 2008, https://doi.org/10.1016/j.bbamem.2007.10.019
  102. Importance of Sphingosine Kinase (SphK) as a Target in Developing Cancer Therapeutics and Recent Developments in the Synthesis of Novel SphK Inhibitors vol.57, pp.13, 2014, https://doi.org/10.1021/jm4011687
  103. Activation of Sphingosine Kinase-1 Mediates Inhibition of Vascular Smooth Muscle Cell Apoptosis by Hyperglycemia vol.56, pp.5, 2007, https://doi.org/10.2337/db06-1418
  104. Activation of sphingosine kinase 2 by endoplasmic reticulum stress ameliorates hepatic steatosis and insulin resistance in mice vol.62, pp.1, 2015, https://doi.org/10.1002/hep.27804
  105. Extracellular and intracellular sphingosine-1-phosphate in cancer vol.30, pp.3-4, 2011, https://doi.org/10.1007/s10555-011-9305-0
  106. Tumor specific cytotoxicity of β-glucosylceramide: structure–cytotoxicity relationship and anti-tumor activity in vivo vol.64, pp.3, 2009, https://doi.org/10.1007/s00280-008-0896-2
  107. Normal neutrophil functions in sphingosine kinase type 1 and 2 knockout mice vol.109, pp.1, 2007, https://doi.org/10.1016/j.imlet.2007.01.001
  108. Molecular Basis of Sphingosine Kinase 1 Substrate Recognition and Catalysis vol.21, pp.5, 2013, https://doi.org/10.1016/j.str.2013.02.025
  109. S1P metabolism in cancer and other pathological conditions vol.92, pp.6, 2010, https://doi.org/10.1016/j.biochi.2010.02.014
  110. Overexpression of sphingosine kinase 1 in liver reduces triglyceride content in mice fed a low but not high-fat diet vol.1851, pp.2, 2015, https://doi.org/10.1016/j.bbalip.2014.12.002
  111. Structure and catalytic function of sphingosine kinases: Analysis by site-directed mutagenesis and enzyme kinetics vol.1831, pp.1, 2013, https://doi.org/10.1016/j.bbalip.2012.09.006
  112. Design, synthesis and evaluation of 2-aminothiazole derivatives as sphingosine kinase inhibitors vol.22, pp.19, 2014, https://doi.org/10.1016/j.bmc.2014.07.044
  113. Regulation and functional roles of sphingosine kinases vol.374, pp.5-6, 2007, https://doi.org/10.1007/s00210-007-0132-3
  114. sphingosine 1-phosphate receptor knockout mice vol.292, pp.1, 2007, https://doi.org/10.1152/ajpregu.00085.2006
  115. Apoptosis induces expression of sphingosine kinase 1 to release sphingosine-1-phosphate as a “come-and-get-me” signal vol.22, pp.8, 2008, https://doi.org/10.1096/fj.08-107169
  116. The investigation of ceranib-2 on apoptosis and drug interaction with carboplatin in human non small cell lung cancer cells in vitro vol.70, pp.1, 2018, https://doi.org/10.1007/s10616-017-0154-8
  117. Cancer Prevention and Therapy with Polyphenols: Sphingolipid-Mediated Mechanisms vol.10, pp.7, 2018, https://doi.org/10.3390/nu10070940
  118. An intrinsic lipid-binding interface controls sphingosine kinase 1 function vol.59, pp.3, 2018, https://doi.org/10.1194/jlr.M081307
  119. The Role of S1P and the Related Signaling Pathway in the Development of Tissue Fibrosis vol.9, pp.1663-9812, 2019, https://doi.org/10.3389/fphar.2018.01504