Skip to main content
SpringerLink
Log in

Role of Lysophospholipids in Cell Growth and Survival

  • Chapter
Apoptosis, Cell Signaling, and Human Diseases

  • 914 Accesses

Summary

Lysophospholipids are not only metabolites in membrane phospholipid synthesis, but also extracellular bioactive mediators of multiple biological processes. The best characterized of these are lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P), which have both emerged as important regulators of cell growth and survival. Identification of LPA and S1P receptors in the past several years has led to the accumulation of evidence that most cellular responses to LPA and S1P are mediated through activation of their cognate G protein-coupled receptors (GPCR). There are at least three high-affinity receptors for LPA—named LPA1, LPA2 and LPA3—and five receptor subtypes for S1P, designated S1P1–5. The widespread expression of these receptors and their downstream G proteins of various classes allow activation of a variety of signal transduction pathways that are integrated to trigger diverse cellular responses to LPA or S1P.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Pages C, Simon MF, Valet P, Saulnier-Blache JS. Lysophosphatidic acid synthesis and release. Prostaglandins Other Lipid Mediat 2001;64:1–10.

    Article  PubMed  CAS  Google Scholar 

  2. van Dijk MC, Postma F, Hilkmann H, Jalink K, van Blitterswijk WJ, Moolenaar WH. Exogenous phospholipase D generates lysophosphatidic acid and activates Ras, Rho and Ca2+ signaling pathways. Curr Biol 1998;8:386–392.

    Article  PubMed  Google Scholar 

  3. Eder AM, Sasagawa T, Mao M, Aoki J, Mills GB. Constitutive and lysophosphatidic acid (LPA)-induced LPA production: role of phospholipase D and phospholipase A2. Clin Cancer Res 2000;6:2482–2491.

    PubMed  CAS  Google Scholar 

  4. Fang X Schummer M Mao M et al. Lysophosphatidic acid is a bioactive mediator in ovarian cancer. Biochim Biophys Acta 2002;1582:257–264

    PubMed  CAS  Google Scholar 

  5. Gesta S, Simon MF, Rey A, et al. Secretion of a lysophospholipase D activity by adipocytes: involvement in lysophosphatidic acid synthesis. J Lipid Res 2002;43:904–910.

    PubMed  CAS  Google Scholar 

  6. Xie Y, Gibbs TC, Mukhin YV, Meier KE. Role for 18:1 lysophosphatidic acid as an autocrine mediator in prostate cancer cells. J Biol Chem 2002;277:32,516–32,526.

    Article  PubMed  CAS  Google Scholar 

  7. Sano T, Baker D, Virag T, et al. Multiple mechanisms linked to platelet activation result in lysophosphatidic acid and sphingosine 1-phosphate generation in blood. J Biol Chem 2002;277:21,197–21,206.

    Article  PubMed  CAS  Google Scholar 

  8. Umezu-Goto M, Kishi Y, Taira A, et al. Autotaxin has lysophospholipase D activity leading to tumor cell growth and motility by lysophosphatidic acid production. J Cell Biol 2002;158:227–233.

    Article  PubMed  CAS  Google Scholar 

  9. Tokumura A, Majima E, Kariya Y, et al. Identification of human plasma lysophospholipase D, a lysophosphatidic acid-producing enzyme, as autotaxin, a multifunctional phosphodiesterase. J Biol Chem 2002;277:39,436–39,442.

    Article  PubMed  CAS  Google Scholar 

  10. Stracke ML, Clair T, Liotta LA. Autotaxin, tumor motility-stimulating exophosphodiesterase. Adv Enzyme Regul 1997;37:135–144.

    Article  PubMed  CAS  Google Scholar 

  11. Imamura F, Horai T, Mukai M, Shinkai K, Sawada M, Akedo H. Induction of in vitro tumor cell invasion of cellular monolayers by lysophosphatidic acid or phospholipase D. Biochem Biophys Res Commun 1993;193:497–503.

    Article  PubMed  CAS  Google Scholar 

  12. Shim YH, Lin CH, Strickland KP. The purification and properties of monoacylglycerol kinase from bovine brain. Biochem Cell Biol 1989;67:233–241.

    Article  PubMed  CAS  Google Scholar 

  13. Bektas M, Payne SG, Liu H, Milstien S, Spiegel S. A novel acylglycerol kinase that produces lysophosphatidic acid modulates crosstalk with EGFR in prostate cancer cells. J Cell Biol 2005;169:801–811.

    Article  PubMed  CAS  Google Scholar 

  14. Reutens AT, Begley CG. Endophilin-1: a multifunctional protein. Int J Biochem Cell Biol 2002;34:1173–1177.

    Article  PubMed  CAS  Google Scholar 

  15. Thompson FJ, Clark MA. Purification of a lysophosphatidic acid-hydrolysing lysophospholipase from rat brain. Biochem J 1994;300:457–461.

    PubMed  CAS  Google Scholar 

  16. Roberts R, Sciorra VA, Morris AJ. Human type 2 phosphatidic acid phosphohydrolases. Substrate specificity of the type 2a, 2b, and 2c enzymes and cell surface activity of the 2a isoform. J Biol Chem 1998;273:22,059–22,067.

    Article  PubMed  CAS  Google Scholar 

  17. Hooks SB, Santos WL, Im DS, Heise CE, Macdonald TL, Lynch KR. Lysophosphatidic acid induced mitogenesis is regulated by lipid phosphate phosphatases and is Edgreceptor independent. J Biol Chem 2001;276:4611–4621.

    Article  PubMed  CAS  Google Scholar 

  18. Sciorra VA, Morris AJ. Roles for lipid phosphate phosphatases in regulation of cellular signaling. Biochim Biophys Acta 2002;1582:45–51.

    PubMed  CAS  Google Scholar 

  19. Brindley DN. Lipid phosphate phosphatases and related proteins: Signaling functions in development, cell division, and cancer. J Cell Biochem 2004;92:900–912.

    Article  PubMed  CAS  Google Scholar 

  20. Smyth SS, Sciorra VA, Sigal YJ, et al. Lipid phosphate phosphatases regulate lysophosphatidic acid production and signaling in platelets: studies using chemical inhibitors of lipid phosphate phosphatase activity. J Biol Chem 2003;278:43,214–43,223.

    Article  PubMed  CAS  Google Scholar 

  21. Maceyka M, Payne SG, Milstien S, Spiegel S. Sphingosine kinase, sphingosine-1-phosphate, and apoptosis. Biochim Biophys Acta 2002;1585:193–201.

    PubMed  CAS  Google Scholar 

  22. Merrill AH, Jr. De novo sphingolipid biosynthesis: a necessary, but dangerous, pathway. J Biol Chem 2002;277:25,843–25,846.

    Article  PubMed  CAS  Google Scholar 

  23. Le Stunff H, Peterson C, Thornton R, Milstien S, Mandala SM, Spiegel S. Characterization of murine sphingosine-1-phosphate phosphohydrolase. J Biol Chem 2002;277:8920–8917.

    Article  PubMed  CAS  Google Scholar 

  24. Ogawa C, Kihara A, Gokoh M, Igarashi Y. Identification and characterization of a novel human sphingosine-1-phosphate phosphohydrolase, hSPP2. J Biol Chem 2003;278:1268–1272.

    Article  PubMed  CAS  Google Scholar 

  25. Pyne S, Pyne NJ. Sphingosine 1-phosphate signalling in mammalian cells. Biochem J 2000;349:385–402.

    Article  PubMed  CAS  Google Scholar 

  26. Kohama T, Olivera A, Edsall L, Nagiec MM, Dickson R, Spiegel S. Molecular cloning and functional characterization of murine sphingosine kinase. J Biol Chem 1998;273:23,722–23,728.

    Article  PubMed  CAS  Google Scholar 

  27. Liu H, Sugiura M, Nava VE, et al. Molecular cloning and functional characterization of a novel mammalian sphingosine kinase type 2 isoform. J Biol Chem 2000;275:19,513–19,520.

    Article  PubMed  CAS  Google Scholar 

  28. Olivera A, Spiegel S. Sphingosine-1-phosphate as a second messenger in cell proliferation induced by PDGF and FCS mitogens. Nature 1993;365:557–560.

    Article  PubMed  CAS  Google Scholar 

  29. Edsall LC, Pirianov GG, Spiegel S. Involvement of sphingosine 1-phosphate in nerve growth factor-mediated neuronal survival and differentiation. J Neurosci 1997;17:6952–6960.

    PubMed  CAS  Google Scholar 

  30. Meyer zu Heringdorf D, Lass H, Alemany R, et al. Sphingosine kinase-mediated Ca2+ signalling by G-protein-coupled receptors. EMBO J 1998;17:2830–2837.

    Article  Google Scholar 

  31. Alemany R, Sichelschmidt B, zu Heringdorf DM, Lass H, van Koppen CJ, Jakobs KH. Stimulation of sphingosine-1-phosphate formation by the P2Y(2) receptor in HL-60 cells: Ca(2+) requirement and implication in receptor-mediated Ca(2+) mobilization, but not MAP kinase activation. Mol Pharmacol 2000;58:491–497.

    PubMed  CAS  Google Scholar 

  32. Melendez A, Floto RA, Gillooly DJ, Harnett MM, Allen JM. FcgRI coupling to phospholipase D initiates sphingosine kinase-mediated calcium mobilization and vesicular trafficking. J Biol Chem 1998;273:9393–9402.

    Article  PubMed  CAS  Google Scholar 

  33. Chuang FY, Sassaroli M, Unkeless JC. Convergence of Fc gamma receptor IIA and Fc gamma receptor IIIB signaling pathways in human neutrophils. J Immunol 2000;164:350–360.

    PubMed  CAS  Google Scholar 

  34. Prieschl EE, Csonga R, Novotny V, Kikuchi GE, Baumruker T. The balance between sphingosine and sphingosine-1-phosphate is decisive for mast cell activation after Fc epsilon receptor I triggering. J Exp Med 1999;190:1–8.

    Article  PubMed  CAS  Google Scholar 

  35. Jolly PS, Bektas M, Olivera A, et al. Transactivation of sphingosine-1-phosphate receptors by Fc(epsilon)RI triggering is required for normal mast cell degranulation and chemotaxis. J Exp Med 2004;199:959–970.

    Article  PubMed  CAS  Google Scholar 

  36. Mazurek N, Megidish T, Hakomori S-I, Igarashi Y. Regulatory effect of phorbol esters on sphingosine kinase in BALB/C 3T3 fibroblasts (variant A31): demonstration of cell typespecific response. Biochem Biophys Res Commun 1994;198:1–9.

    Article  PubMed  CAS  Google Scholar 

  37. Xia P, Gamble JR, Rye KA, et al. Tumor necrosis factor-a induces adhesion molecule expression through the sphingosine kinase pathway. Proc Natl Acad Sci USA 1998;95:14,196–14,201.

    Article  PubMed  CAS  Google Scholar 

  38. Olivera A, Kohama T, Edsall LC, et al. Sphingosine kinase expression increases intracellular sphingosine-1-phosphate and promotes cell growth and survival. J Cell Biol 1999;147:545–558.

    Article  PubMed  CAS  Google Scholar 

  39. Liu H, Toman RE, Goparaju S, et al. Sphingosine kinase type 2 is a putative BH3-Only protein that induces apoptosis. J Biol Chem 2003;278:40,330–40,336.

    Article  PubMed  CAS  Google Scholar 

  40. Igarashi N, Okada T, Hayashi S, Fujita T, Jahangeer S, Nakamura SI. Sphingosine kinase 2 is a nuclear protein and inhibits DNA synthesis. J Biol Chem 2003;278:46,832–46,839.

    Article  PubMed  CAS  Google Scholar 

  41. Olivera A, Edsall L, Poulton S, Kazlauskas A, Spiegel S. Platelet-derived growth factor-induced activation of sphingosine kinase requires phosphorylation of the PDGF receptor tyrosine residue responsible for binding of PLCgamma. FASEB J 1999;13:1593–1600.

    PubMed  CAS  Google Scholar 

  42. van Koppen CJ, Meyerzu Heringdorf D, Alemany R, Jakobs KH. Sphingosine kinasemediated calcium signaling by muscarinic acetylcholine receptors. Life Sci 2001;68:2535–2540.

    Article  PubMed  Google Scholar 

  43. Young KW, Willets JM, Parkinson MJ, et al. Ca2+/calmodulin-dependent translocation of sphingosine kinase: role in plasma membrane relocation but not activation. Cell Calcium 2003;33:119–128.

    Article  PubMed  CAS  Google Scholar 

  44. Gijsbers S, Van der Hoeven G, Van Veldhoven PP. Subcellular study of sphingoid base phosphorylation in rat tissues: evidence for multiple sphingosine kinases. Biochim Biophys Acta 2001;1532:37–50.

    PubMed  CAS  Google Scholar 

  45. Rosenfeldt HM, Hobson JP, Maceyka M, et al. EDG-1 links the PDGF receptor to Src and focal adhesion kinase activation leading to lamellipodia formation and cell migration. FASEB J 2001;15:2649–2659.

    Article  PubMed  CAS  Google Scholar 

  46. Melendez AJ, Ibrahim FB. Antisense knockdown of sphingosine kinase 1 in human macrophages inhibits c5a receptor-dependent signal transduction, Ca2+ signals, enzyme release, cytokine production, and chemotaxis. J Immunol 2004;173:1596–1603.

    PubMed  CAS  Google Scholar 

  47. Johnson KR, Becker KP, Facchinetti MM, Hannun YA, Obeid LM. 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 2002;277:35,257–35,262.

    Article  PubMed  CAS  Google Scholar 

  48. Olivera A, Rosenthal J, Spiegel S. Effect of acidic phospholipids on sphingosine kinase. J Cell Biochem 1996;60:529–537.

    Article  PubMed  CAS  Google Scholar 

  49. Shu X, Wu W, Mosteller RD, Broek D. Sphingosine kinase mediates vascular endothelial growth factor-induced activation of ras and mitogen-activated protein kinases. Mol Cell Biol 2002;22:7758–7768.

    Article  PubMed  CAS  Google Scholar 

  50. Pitson SM, Moretti PA, Zebol JR, et al. Activation of sphingosine kinase 1 by ERK1/2-mediated phosphorylation. EMBO J 2003;22:5491–5500.

    Article  PubMed  CAS  Google Scholar 

  51. Pitson SM, Xia P, Leclercq TM, et al. Phosphorylation-dependent translocation of sphingosine kinase to the plasma membrane drives its oncogenic signalling. J Exp Med 2005;201:49–54.

    Article  PubMed  CAS  Google Scholar 

  52. Delon C, Manifava M, Wood E, et al. Sphingosine kinase 1 is an intracellular effector of phosphatidic acid. J Biol Chem 2004;279:44,763–44,774.

    Article  PubMed  CAS  Google Scholar 

  53. Ancellin N, Colmont C, Su J, et al. Extracellular export of sphingosine kinase-1 enzyme: Sphingosine 1-phosphate generation and the induction of angiogenic vascular maturation. J Biol Chem 2002;277:6667–6675.

    Article  PubMed  CAS  Google Scholar 

  54. Clair T, Aoki J, Koh E, et al. Autotaxin hydrolyzes sphingosylphosphorylcholine to produce the regulator of migration, sphingosine-1-phosphate. Cancer Res 2003;63:5446–5453.

    PubMed  CAS  Google Scholar 

  55. Hecht JH, Weiner JA, Post SR, Chun J. Ventricular zone gene-1 (vzg-1) encodes a lysophosphatidic acid receptor expressed in neurogenic regions of the developing cerebral cortex. J Cell Biol 1996;135:1071–1083.

    Article  PubMed  CAS  Google Scholar 

  56. Chun J, Goetzl EJ, Hla T, et al. International Union of Pharmacology. XXXIV. Lysophospholipid Receptor Nomenclature. Pharmacol Rev 2002;54:265–269.

    Article  PubMed  CAS  Google Scholar 

  57. Noguchi K, Ishii S, Shimizu T. Identification of p2y9/GPR23 as a novel G protein-coupled receptor for lysophosphatidic acid, structurally distant from the Edg family. J Biol Chem 2003;278:25,600–25,606.

    Article  PubMed  CAS  Google Scholar 

  58. Hla T, Lee MJ, Ancellin N, Paik JH, Kluk MJ. Lysophospholipids-receptor revelations. Science 2001;294:1875–1878.

    Article  PubMed  CAS  Google Scholar 

  59. Spiegel S, Milstien S. Sphingosine 1-phosphate, a key cell signaling molecule. J Biol Chem 2002;277:25,851–25,854.

    Article  PubMed  CAS  Google Scholar 

  60. Kostenis E. Novel clusters of receptors for sphingosine-1-phosphate, sphingosylphosphorylcholine, and (lyso)-phosphatidic acid: New receptors for “Old” ligands. J Cell Biochem 2004;92:923–936.

    Article  PubMed  CAS  Google Scholar 

  61. Anliker B, Chun J. Lysophospholipid G protein-coupled receptors. J Biol Chem 2004;279:20,555–20,558.

    Article  PubMed  CAS  Google Scholar 

  62. Van Leeuwen FN, Olivo C, Grivell S, Giepmans BN, Collard JG, Moolenaar WH. Rac activation by lysophosphatidic acid LPA1 receptors through the guanine nucleotide exchange factor Tiam1. J Biol Chem 2003;278:400–406.

    Article  PubMed  CAS  Google Scholar 

  63. Radeff-Huang J, Seasholtz TM, Matteo RG, Brown JH. G protein mediated signaling pathways in lysophospholipid induced cell proliferation and survival. J Cell Biochem 2004;92:949–966.

    Article  PubMed  CAS  Google Scholar 

  64. Heldin NE, Paulsson Y, Forsberg K, Heldin CH, Westermark B. Induction of cyclic AMP synthesis by forskolin is followed by a reduction in the expression of c-myc messenger RNA and inhibition of 3H-thymidine incorporation in human fibroblasts. J Cell Physiol 1989;138:17–23.

    Article  PubMed  CAS  Google Scholar 

  65. Magnaldo I, Pouyssegur, Paris S. Cyclic AMP inhibits mitogen-induced DNA synthesis in hamster fibroblasts, regardless of the signalling pathway involved. FEBS Lett 1989;245:65–69.

    Article  PubMed  CAS  Google Scholar 

  66. Fukushima N, Chun J. The LPA receptors. Prostaglandins 2001;64:21–32.

    PubMed  CAS  Google Scholar 

  67. Kranenburg O, Poland M, van Horck FP, Drechsel D, Hall A, Moolenaar WH. Activation of RhoA by lysophosphatidic acid and Galpha12/13 subunits in neuronal cells: induction of neurite retraction. Mol Biol Cell 1999;10:1851–1857.

    PubMed  CAS  Google Scholar 

  68. Ren XD, Kiosses WB, Schwartz MA. Regulation of the small GTP-binding protein Rho by cell adhesion and the cytoskeleton. EMBO J 1999;18:578–585.

    Article  PubMed  CAS  Google Scholar 

  69. Bar-Sagi D, Hall A. Ras and Rho GTPases: a family reunion. Cell 2000;103:227–238.

    Article  PubMed  CAS  Google Scholar 

  70. Marinissen MJ, Chiariello M, Tanos T, Bernard O, Narumiya S, Gutkind JS. The small GTP-binding protein RhoA regulates c-jun by a ROCK-JNK signaling axis. Mol Cell 2004;14:29–41.

    Article  PubMed  CAS  Google Scholar 

  71. Jaffe AB, Hall A, Schmidt A. Association of CNK1 with Rho guanine nucleotide exchange factors controls signaling specificity downstream of Rho. Curr Biol 2005;15:405–412.

    Article  PubMed  CAS  Google Scholar 

  72. Olson MF, Paterson HF, Marshall CJ. Signals from Ras and Rho GTPases interact to regulate expression of p21Waf1/Cip1. Nature 1998;394:295–299.

    Article  PubMed  CAS  Google Scholar 

  73. Pruitt K, Der CJ. Ras and Rho regulation of the cell cycle and oncogenesis. Cancer Lett 2001;171:1–10.

    Article  PubMed  CAS  Google Scholar 

  74. Daub H, Weiss FU, Wallasch C, Ullrich A. Role of transactivation of the EGF receptor in signalling by G-protein-coupled receptors. Nature 1996;379:557–560.

    Article  PubMed  CAS  Google Scholar 

  75. Prenzel N, Zwick E, Daub H, et al. EGF receptor transactivation by G-protein-coupled receptors requires metalloproteinase cleavage of proHB-EGF. Nature 1999;402:884–888.

    PubMed  CAS  Google Scholar 

  76. Baudhuin LM, Jiang Y, Zaslavsky A, Ishii I, Chun J, Xu Y. S1P3-mediated Akt activation and cross-talk with platelet-derived growth factor receptor (PDGFR). FASEB J 2004;18:341–343.

    PubMed  CAS  Google Scholar 

  77. Gschwind A, Prenzel N, Ullrich A. Lysophosphatidic acid-induced squamous cell carcinoma cell proliferation and motility involves epidermal growth factor receptor signal transactivation. Cancer Res 2002;62:6329–6336.

    PubMed  CAS  Google Scholar 

  78. Schafer B, Gschwind A, Ullrich A. Multiple G-protein-coupled receptor signals converge on the epidermal growth factor receptor to promote migration and invasion. Oncogene 2004;23:991–999.

    Article  PubMed  CAS  Google Scholar 

  79. Hobson JP, Rosenfeldt HM, Barak LS, et al. Role of the sphingosine-1-phosphate receptor EDG-1 in PDGF-induced cell motility. Science 2001;291:1800–1803.

    Article  PubMed  CAS  Google Scholar 

  80. Goparaju K, Jolly PS, Watterson KR, et al. The S1P2 Receptor Negatively Regulates PDGF-Induced Motility and Proliferation. Mol Cell Biol 2005;25:4237–4249.

    Article  PubMed  CAS  Google Scholar 

  81. Liu Y, Wada R, Yamashita T, 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.

    PubMed  CAS  Google Scholar 

  82. Lee MJ, Thangada S, Claffey KP, et al. Vascular endothelial cell adherens junction assembly and morphogenesis induced by sphingosine-1-phosphate. Cell 1999;99:301–312.

    Article  PubMed  CAS  Google Scholar 

  83. Wang F, Van Brocklyn JR, Hobson JP, et al. Sphingosine 1-phosphate stimulates cell migration through a G(i)-coupled cell surface receptor. Potential involvement in angiogenesis. J Biol Chem 1999;274:35,343–35,350.

    Article  PubMed  CAS  Google Scholar 

  84. Toman RE, Payne SG, Watterson K, et al. Differential transactivation of sphingosine-1-phosphate receptors modulates nerve gowth factor-induced neurite extension. J Cell Biol 2004;166:381–392.

    Article  PubMed  CAS  Google Scholar 

  85. Van Corven EJ, Groenink A, Jalink K, Eicholtz T, Moolenaar WH. Lysophosphatidateinduced cell proliferation: Identification and dissection of signaling pathways mediated by G proteins. Cell 1989;59:45–54.

    Article  PubMed  Google Scholar 

  86. Zhang H, Desai NN, Olivera A, Seki T, Brooker G, Spiegel S. Sphingosine-1-phosphate, a novel lipid, involved in cellular proliferation. J Cell Biol 1991;114:155–167.

    Article  PubMed  CAS  Google Scholar 

  87. Desai NN, Spiegel S. Sphingosylphosphorylcholine is a remarkably potent mitogen for a variety of cell lines. Biochem Biophys Res Commun 1991;181:361–366.

    Article  PubMed  CAS  Google Scholar 

  88. van Corven EJ, vanRijswijk A, Jalink K, van der Bend RL, van Blitterswijk WJ, Moolenaar WH. Mitogenic action of lysophosphatidic acid and phosphatidic acid on fibroblasts. Dependence on acyl-chain length and inhibition by suramin. Biochem J 1992;281:163–169.

    PubMed  Google Scholar 

  89. Fang X, Gaudette D, Furui T, et al. Lysophospholipid growth factors in the initiation, progression, metastases, and management of ovarian cancer. Ann NY Acad Sci 2000;905:188–208.

    Article  PubMed  CAS  Google Scholar 

  90. Tanyi JL, Morris AJ, Wolf JK, et al. The human lipid phosphate phosphatase-3 decreases the growth, survival, and tumorigenesis of ovarian cancer cells: validation of the lysophosphatidic acid signaling cascade as a target for therapy in ovarian cancer. Cancer Res 2003;63:1073–1082.

    PubMed  CAS  Google Scholar 

  91. Hasegawa Y, Erickson JR, Goddard GJ, et al. Identification of a phosphothionate analogue of lysophosphatidic acid (LPA) as a selective agonist of the LPA3 receptor. J Biol Chem 2003;278:11,962–11,969.

    Article  PubMed  CAS  Google Scholar 

  92. Pebay A, Toutant M, Premont J, et al. Sphingosine-1-phosphate induces proliferation of astrocytes: regulation by intracellular signalling cascades. Eur J Neurosci 2001;13:2067–2076.

    Article  Google Scholar 

  93. Fang X, Yu S, LaPushin R, et al. Lysophosphatidic acid prevents apoptosis in fibroblastsvia G(i)-protein-mediated activation of mitogen-activated protein kinase. Biochem J 2000;352:135–143.

    Article  PubMed  CAS  Google Scholar 

  94. Rozengurt E. Early signals in the mitogenic response. Science 1986;234:161–166.

    Article  PubMed  CAS  Google Scholar 

  95. Dumont JE, Jauniaux JC, Roger PP. The cyclic AMP-mediated stimulation of cell proliferation. Trends Biochem Sci 1989;14:67–71.

    Article  PubMed  CAS  Google Scholar 

  96. Cook SJ, McCormick F. Kinetic and biochemical correlation between sustained p44ERK1 (44 kDa extracellular signal-regulated kinase 1) activation and lysophosphatidic acidstimulated DNA synthesis in Rat-1 cells. Biochem J 1996;320:237–245.

    PubMed  CAS  Google Scholar 

  97. Van Brocklyn JR, Behbahani B, Lee NH. Homodimerization and heterodimerization of S1P/EDG sphingosine-1-phosphate receptors. Biochim Biophys Acta 2002;1582:89–93.

    PubMed  Google Scholar 

  98. Kranenburg O, Moolenaar WH. Ras-MAP kinase signaling by lysophosphatidic acid and other G protein-coupled receptor agonists. Oncogene 2001;20:1540–1546.

    Article  PubMed  CAS  Google Scholar 

  99. Cook SJ, McCormick F. Inhibition by cAMP of Ras-dependent activation of Raf. Science 1993;262:1069–1072.

    Article  PubMed  CAS  Google Scholar 

  100. Fleming IN, Batty IH, Prescott AR, et al. Inositol phospholipids regulate the guaninenucleotide-exchange factor Tiam1 by facilitating its binding to the plasma membrane and regulating GDP/GTP exchange on Rac1. Biochem J 2004;382:857–865.

    Article  PubMed  CAS  Google Scholar 

  101. Fleming IN, Gray A, Downes CP. Regulation of the Rac1-specific exchange factor Tiam1 involves both phosphoinositide 3-kinase-dependent and-independent components. Biochem J 2000;351:173–182.

    Article  PubMed  CAS  Google Scholar 

  102. Joyce D, Bouzahzah B, Fu M, et al. Integration of Rac-dependent regulation of cyclin D1 transcription through a nuclear factor-kappaB-dependent pathway. J Biol Chem 1999;274:25,245–25,249.

    Article  PubMed  CAS  Google Scholar 

  103. Welsh CF, Roovers K, Villanueva J, Liu Y, Schwartz MA, Assoian RK. Timing of cyclin D1 expression within G1 phase is controlled by Rho. Nat Cell Biol 2001;3:950–957.

    Article  PubMed  CAS  Google Scholar 

  104. Babior BM. NADPH oxidase. Curr Opin Immunol 2004;16:42–47.

    Article  PubMed  CAS  Google Scholar 

  105. Fukushima N, Kimura Y, Chun J. A single receptor encoded by vzg-1/lpA1/edg-2 couples to G proteins and mediates multiple cellular responses to lysophosphatidic acid. Proc Natl Acad Sci USA 1998;95:6151–6156.

    Article  PubMed  CAS  Google Scholar 

  106. An S, Zheng Y, Bleu T. Sphingosine 1-phosphate-induced cell proliferation, survival, and related signaling events mediated by G protein-coupled receptors Edg3 and Edg5. J Biol Chem 2000;275:288–296.

    Article  PubMed  CAS  Google Scholar 

  107. Fang X, Yu S, Bast RC, et al. Mechanisms for lysophosphatidic acid-induced cytokine production in ovarian cancer cells. J Biol Chem 2004;279:9653–9661.

    Article  PubMed  CAS  Google Scholar 

  108. Katsuma S, Hada Y, Ueda T, et al. Signalling mechanisms in sphingosine 1-phosphatepromoted mesangial cell proliferation. Genes Cells 2002;7:1217–1230.

    Article  PubMed  CAS  Google Scholar 

  109. Contos JJ, Ishii I, Fukushima N, et al. Characterization of lpa(2) (Edg4) and lpa(1)/lpa(2) (Edg2/Edg4) lysophosphatidic acid receptor knockout mice: signaling deficits without obvious phenotypic abnormality attributable to lpa(2). Mol Cell Biol 2002;22:6921–6929.

    Article  PubMed  CAS  Google Scholar 

  110. Olivera A, Rosenfeldt HM, Bektas M, 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;278:46,452–46,460.

    Article  PubMed  CAS  Google Scholar 

  111. Tigyi G, Dyer DL, Miledi R. Lysophosphatidic acid possesses dual action in cell proliferation. Proc Natl Acad Sci USA 1994;91:1908–1912.

    Article  PubMed  CAS  Google Scholar 

  112. Sauer B, Vogler R, von Wenckstern H, et al. Involvement of Smad signaling in sphingosine 1-phosphate-mediated biological responses of keratinocytes. J Biol Chem 2004;279:38,471–38,479.

    Article  PubMed  CAS  Google Scholar 

  113. Kim DS, Kim SY, Kleuser B, Schafer-Korting M, Kim KH, Park KC. Sphingosine-1-phosphate inhibits human keratinocyte proliferation via Akt/protein kinase B inactivation. Cell Signal 2004;16:89–95.

    Article  PubMed  CAS  Google Scholar 

  114. Ikeda H, Satoh H, Yanase M, et al. Antiproliferative property of sphingosine 1-phosphate in rat hepatocytes involves activation of Rho via Edg-5. Gastroenterology 2003;124:459–469.

    Article  PubMed  CAS  Google Scholar 

  115. Jin Y, Knudsen E, Wang L, et al. Sphingosine 1-phosphate is a novel inhibitor of T-cell proliferation. Blood 2003;101:4909–4915.

    Article  PubMed  CAS  Google Scholar 

  116. Frankel A, Mills GB. Peptide and lipid growth factors decrease cis-diamminedichloroplatinum-induced cell death in human ovarian cancer cells. Clin Cancer Res 1996;2:1307–1313.

    PubMed  CAS  Google Scholar 

  117. Deng W, Balazs L, Wang DA, Van Middlesworth L, Tigyi G, Johnson LR. Lysophosphatidic acid protects and rescues intestinal epithelial cells from radiation-andchemotherapy-induced apoptosis. Gastroenterology 2002;123:206–216.

    Article  PubMed  CAS  Google Scholar 

  118. Weiner JA, Chun J. Schwann cell survival mediated by the signaling phospholipid lysophosphatidic acid. Proc Natl Acad Sci USA 1999;96:5233–5238.

    Article  PubMed  CAS  Google Scholar 

  119. Li Y, Gonzalez MI, Meinkoth JL, Field J, Kazanietz MG, Tennekoon GI. Lysophosphatidic acid promotes survival and differentiation of rat Schwann cells. J Biol Chem 2003;278:9585–9591.

    Article  PubMed  CAS  Google Scholar 

  120. Koh JS, Lieberthal W, Heydrick S, Levine JS. Lysophosphatidic acid is a major serum noncytokine survival factor for murine macrophages which acts via the phosphatidylinositol 3-kinase signaling pathway. J Clin Invest 1998;102:716–727.

    Article  PubMed  CAS  Google Scholar 

  121. Goetzl EJ, Kong Y, Mei B. Lysophosphatidic acid and sphingosine 1-phosphate protection of T cells from apoptosis in association with suppression of Bax. J Immunol 1999;162:2049–2056.

    PubMed  CAS  Google Scholar 

  122. Karliner JS, Honbo N, Summers K, Gray MO, Goetzl EJ. The lysophospholipids sphingosine-1-phosphate and lysophosphatidic acid enhance survival during hypoxia in neonatal rat cardiac myocytes. J Mol Cell Cardiol 2001;33:1713–1717.

    Article  PubMed  CAS  Google Scholar 

  123. Grey A, Chen Q, Callon K, Xu X, Reid IR, Cornish J. The phospholipids sphingosine-1-phosphate and lysophosphatidic acid prevent apoptosis in osteoblastic cells via a signaling pathway involving G(i) proteins and phosphatidylinositol-3 kinase. Endocrinology 2002;143:4755–4763.

    Article  PubMed  CAS  Google Scholar 

  124. Levine JS, Koh JS, Triaca V, Lieberthal W. Lysophosphatidic acid: a novel growth and survival factor for renal proximal tubular cells. Am J Physiol 1997;273:F575–F585.

    PubMed  CAS  Google Scholar 

  125. Raj GV, Sekula JA, Guo R, Madden JF, Daaka Y. Lysophosphatidic acid promotes survival of androgen-insensitive prostate cancer PC3 cells via activation of NF-kappaB. Prostate 2004;61:105–113.

    Article  PubMed  CAS  Google Scholar 

  126. Hu X, Haney N, Kropp D, Kabore AF, Johnston JB, Gibson SB. Lysophosphatidic acid (LPA) protects primary chronic lymphocytic leukemia cells from apoptosis through LPA receptor activation of the anti-apoptotic protein AKT/PKB. J Biol Chem 2005;280:9498–9508.

    Article  PubMed  CAS  Google Scholar 

  127. Meng Y, Graves L, Do TV, So J, Fishman DA. Upregulation of FasL by LPA on ovarian cancer cell surface leads to apoptosis of activated lymphocytes. Gynecol Oncol 2004;95:488–495.

    Article  PubMed  CAS  Google Scholar 

  128. Kang YC, Kim KM, Lee KS, et al. Serum bioactive lysophospholipids prevent TRAILinduced apoptosis via PI3K/Akt-dependent cFLIP expression and Bad phosphorylation. Cell Death Differ 2004;11:1287–1298.

    Article  PubMed  CAS  Google Scholar 

  129. de Vries B, Matthijsen RA, van Bijnen AA, Wolfs TG, Buurman WA. Lysophosphatidic acid prevents renal ischemia-reperfusion injury by inhibition of apoptosis and complement activation. Am J Pathol 2003;163:47–56.

    PubMed  Google Scholar 

  130. Sturm A, Dignass AU. Modulation of gastrointestinal wound repair and inflammation by phospholipids. Biochim Biophys Acta 2002;1582:282–288.

    PubMed  CAS  Google Scholar 

  131. Sautin YY, Crawford JM, Svetlov SI. Enhancement of survival by LPA via Erk1/Erk2 and PI 3-kinase/Akt pathways in a murine hepatocyte cell line. Am J Physiol Cell Physiol 2001;281:C2010–C2019.

    PubMed  CAS  Google Scholar 

  132. Weiner JA, Fukushima N, Contos JJ, Scherer SS, Chun J. Regulation of Schwann cell morphology and adhesion by receptor-mediated lysophosphatidic acid signaling. J Neurosci 2001;21:7069–7078.

    PubMed  CAS  Google Scholar 

  133. Deng W, Wang DA, Gosmanova E, Johnson LR, Tigyi G. LPA protects intestinal epithelial cells from apoptosis by inhibiting the mitochondrial pathway. Am J Physiol Gastrointest Liver Physiol 2003;284:G821–G829.

    PubMed  CAS  Google Scholar 

  134. Baudhuin LM, Cristina KL, Lu J, Xu Y. Akt activation induced by lysophosphatidic acid and sphingosine-1-phosphate requires both mitogen-activated protein kinase kinase and p38 mitogen-activated protein kinase and is cell-line specific. Mol Pharmacol 2002;62:660–671.

    Article  PubMed  CAS  Google Scholar 

  135. Shahrestanifar M, Fan X, Manning DR. Lysophosphatidic acid activates NF-kappaB in fibroblasts. A requirement for multiple inputs. J Biol Chem 1999;274:3828–3833.

    Article  PubMed  CAS  Google Scholar 

  136. Palmetshofer A, Robson SC, Nehls V. Lysophosphatidic acid activates nuclear factor kappa B and induces proinflammatory gene expression in endothelial cells. Thromb Haemost 1999;82:1532–1537.

    PubMed  CAS  Google Scholar 

  137. Lee H, Lin CI, Liao JJ, et al. Lysophospholipids increase ICAM-1 expression in HUVEC through a Gi-and NF-kappaB-dependent mechanism. Am J Physiol Cell Physiol 2004;287:C1657–1666.

    Article  PubMed  CAS  Google Scholar 

  138. Lai JM, Lu CY, Yang-Yen HF, Chang ZF. Lysophosphatidic acid promotes phorbolester-induced apoptosis in TF-1 cells by interfering with adhesion. Biochem J 2001;359:227–233.

    Article  PubMed  CAS  Google Scholar 

  139. Ediger TL, Toews ML. Synergistic stimulation of airway smooth muscle cell mitogenesis. J Pharmacol Exp Ther 2000;294:1076–1082.

    PubMed  CAS  Google Scholar 

  140. Cuvillier O, Pirianov G, Kleuser B, et al. Suppression of ceramide-mediated programmed cell death by sphingosine-1-phosphate. Nature 1996;381:800–803.

    Article  PubMed  CAS  Google Scholar 

  141. Morita Y, Perez GI, Paris F, et al. Oocyte apoptosis is suppressed by disruption of the acid sphingomyelinase gene or by sphingosine-1-phosphate therapy. Nature Med 2000;6:1109–1114.

    Article  PubMed  CAS  Google Scholar 

  142. Edsall LC, Cuvillier O, Twitty S, Spiegel S, Milstien S. Sphingosine kinase expression regulates apoptosis and caspase activation in PC12 cells. J Neurochem 2001;76:1573–1584.

    Article  PubMed  CAS  Google Scholar 

  143. Morales-Ruiz M, Lee MJ, Zollner S, et al. Sphingosine 1-phosphate activates Akt, nitric oxide production, and chemotaxis through a Gi protein/phosphoinositide 3-kinase pathway in endothelial cells. J Biol Chem 2001;276:19,672–19,677.

    Article  PubMed  CAS  Google Scholar 

  144. Limaye VS, Li X, Hahn C, et al. 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 2005;105:3169–3177.

    Article  PubMed  CAS  Google Scholar 

  145. Bektas M, Jolly PS, Muller C, Eberle J, Spiegel S, Geilen CC. Sphingosine kinase activity counteracts ceramide-mediated cell death in human melanoma cells: role of Bcl-2 expression. Oncogene 2005;24:178–187.

    Article  PubMed  CAS  Google Scholar 

  146. Kim DS, Kim SY, Lee JE, et al. Sphingosine-1-phosphate-induced ERK activation protects human melanocytes from UVB-induced apoptosis. Arch Pharm Res 2003;26:739–746.

    Article  PubMed  CAS  Google Scholar 

  147. Siehler S, Wang Y, Fan X, Windh RT, Manning DR. Sphingosine 1-phosphate activates nuclear factor-kappa B through Edg receptors. Activation through Edg-3 and Edg-5, but not Edg-1, in human embryonic kidney 293 cells. J Biol Chem 2001;276:48,733–48,739.

    Article  PubMed  CAS  Google Scholar 

  148. Rani CS, Berger A, Wu J, et al. Divergence in signal transduction pathways of PDGF and EGF receptors: Involvement of sphingosine-1-phosphate in PDGF but not EGF signaling. J Biol Chem 1997;272:10,777–10,783.

    Article  PubMed  CAS  Google Scholar 

  149. Wu W, Shu X, Hovsepyan H, Mosteller RD, Broek D. VEGF receptor expression and signaling in human bladder tumors. Oncogene 2003;22:3361–3370.

    Article  PubMed  CAS  Google Scholar 

  150. Van Brocklyn JR, Lee MJ, Menzeleev R, et al. Dual actions of sphingosine-1-phosphate: extracellular through the Gi-coupled orphan receptor edg-1 and intracellular to regulate proliferation and survival. J Cell Biol 1998;142:229–240.

    Article  PubMed  Google Scholar 

  151. Paris F, Perez GI, Fuks Z, et al. Sphingosine 1-phosphate preserves fertility in irradiated emale mice without propagating genomic damage in offspring. Nature Med 2002;8:901–902.

    Article  PubMed  CAS  Google Scholar 

  152. Mandala SM, Thornton R, Tu Z, et al. Sphingoid base 1-phosphate phosphatase: a key regulator of sphingolipid metabolism and stress response. Proc Natl Acad Sci USA 1998;95:150–155.

    Article  PubMed  CAS  Google Scholar 

  153. Mao C, Saba JD, Obeid LM. The dihydrosphingosine-1-phosphate phosphatases of Saccharomyces cerevisiae are important regulators of cell proliferation and heat stress responses. Biochem J 1999;342:667–675.

    Article  PubMed  CAS  Google Scholar 

  154. Ng CK, Carr K, McAinsh MR, Powell B, Hetherington AM. Drought-induced guard cell signal transduction involves sphingosine-1-phosphate. Nature 2001;410:596–599.

    Article  PubMed  CAS  Google Scholar 

  155. Coursol S, Fan LM, Le Stunff H, Spiegel S, Gilroy S, Assmann SM. Sphingolipid signalling in Arabidopsis guard cells involves heterotrimeric G proteins. Nature 2003;423:651–654.

    Article  PubMed  CAS  Google Scholar 

  156. Fernhout BJ, Dijcks FA, Moolenaar WH, Ruigt GS. Lysophosphatidic acid induces inward currents in Xenopus laevis oocytes; evidence for an extracellular site of action. Eur J Pharmacol 1992;213:313–315.

    Article  PubMed  CAS  Google Scholar 

  157. Zhang C, Baker DL, Yasuda S, et al. Lysophosphatidic acid induces neointima formation through PPARγ activation. J Exp Med 2004;199:763–774.

    Article  PubMed  CAS  Google Scholar 

  158. McIntyre TM, Pontsler AV, Silva AR, et al. Identification of an intracellular receptor for lysophosphatidic acid (LPA): LPA is a transcellular PPARgamma agonist. Proc Natl Acad Sci USA 2003;100:131–136.

    Article  PubMed  CAS  Google Scholar 

  159. Saez E, Rosenfeld J, Livolsi A, et al. PPAR gamma signaling exacerbates mammary gland tumor development. Genes Dev 2004;18:528–540.

    Article  PubMed  CAS  Google Scholar 

  160. Bagga S, Price KS, Lin DA, Friend DS, Austen KF, Boyce JA. Lysophosphatidic acid accelerates the development of human mast cells. Blood 2004;104:4080–4087.

    Article  PubMed  CAS  Google Scholar 

  161. Baker DL, Desiderio DM, Miller DD, Tolley B, Tigyi GJ. Direct quantitative analysis of lysophosphatidic acid molecular species by stable isotope dilution electrospray ionization liquid chromatography-mass spectrometry. Anal Biochem 2001;292:287–295.

    Article  PubMed  CAS  Google Scholar 

  162. Yatomi Y, Ozaki Y, Ohmori T, Igarashi Y. Sphingosine 1-phosphate: synthesis and release. Prostaglandins Other Lipid Mediat 2001;64:107–122.

    Article  PubMed  CAS  Google Scholar 

  163. Okajima F. Plasma lipoproteins behave as carriers of extracellular sphingosine 1-phosphate: is this an atherogenic mediator or an anti-atherogenic mediator? Biochim Biophys Acta 2002;1582:132–137.

    PubMed  CAS  Google Scholar 

  164. Balazs L, Okolicany J, Ferrebee M, Tolley B, Tigyi G. Topical application of the phospholipid growth factor lysophosphatidic acid promotes wound healing in vivo. Am J Physiol Regul Integr Comp Physiol 2001;280:R466–R472.

    PubMed  CAS  Google Scholar 

  165. Abe M, Ho CH, Kamm KE, Grinnell F. Different molecular motors mediate plateletderived growth factor and lysophosphatidic acid-stimulated floating collagen matrix contraction. J Biol Chem 2003;278:47,707–47,712.

    Article  PubMed  CAS  Google Scholar 

  166. van Leeuwen FN, Giepmans BN, van Meeteren LA, Moolenaar WH. Lysophosphatidic acid: mitogen and motility factor. Biochem Soc Trans 2003;31:1209–1212.

    PubMed  Google Scholar 

  167. Lee H, Goetzl EJ, An S. Lysophosphatidic acid and sphingosine 1-phosphate stimulate endothelial cell wound healing. Am J Physiol Cell Physiol 2000;278:C612–C618.

    PubMed  CAS  Google Scholar 

  168. Xu Y, Gaudette DC, Boynton JD, et al. Characterization of an ovarian cancer activating factor in ascites from ovarian cancer patients. Clin Cancer Res 1995;1:1223–1232.

    PubMed  CAS  Google Scholar 

  169. Pustilnik TB, Estrella V, Wiener JR, et al. Lysophosphatidic acid induces urokinase secretion by ovarian cancer cells. Clin Cancer Res 1999;5:3704–3710.

    PubMed  CAS  Google Scholar 

  170. Hu YL, Tee MK, Goetzl EJ, et al. Lysophosphatidic acid induction of vascular endothelial growth factor expression in human ovarian cancer cells. J Natl Cancer Inst 2001;93:762–768.

    Article  PubMed  CAS  Google Scholar 

  171. Schwartz BM, Hong G, Morrison BH, et al. Lysophospholipids increase interleukin-8expression in ovarian cancer cells. Gynecol Oncol 2001;81:291–300.

    Article  PubMed  CAS  Google Scholar 

  172. Shida D, Watanabe T, Aoki J, et al. Aberrant expression of lysophosphatidic acid (LPA) receptors in human colorectal cancer. Lab Invest 2004;84:1352–1362.

    Article  PubMed  CAS  Google Scholar 

  173. Yun CC, Sun H, Wang D, et al. The LPA2 receptor mediates mitogenic signals in human colon cancer cells. Am J Physiol Cell Physiol 2005;289:C2–C11.

    Article  PubMed  CAS  Google Scholar 

  174. Schulte KM, Beyer A, Kohrer K, Oberhauser S, Roher HD. Lysophosphatidic acid, a novel lipid growth factor for human thyroid cells: over-expression of the high-affinity receptor edg4 in differentiated thyroid cancer. Int J Cancer 2001;92:249–256.

    Article  PubMed  CAS  Google Scholar 

  175. Kitayama J, Shida D, Sako A, et al. Over-expression of lysophosphatidic acid receptor-2 in human invasive ductal carcinoma. Breast Cancer Res 2004;6:R640–R646.

    Article  PubMed  CAS  Google Scholar 

  176. Boucharaba A, Serre CM, Gres S, et al. Platelet-derived lysophosphatidic acid supports the progression of osteolytic bone metastases in breast cancer. J Clin Invest 2004;114:1714–1725.

    Article  PubMed  CAS  Google Scholar 

  177. Xia P, Gamble JR, Wang L, et al. An oncogenic role of sphingosine kinase. Curr Biol 2000;10:1527–1530.

    Article  PubMed  CAS  Google Scholar 

  178. Nava VE, Hobson JP, Murthy S, Milstien S, Spiegel S. Sphingosine kinase type 1 promotes estrogen-dependent tumorigenesis of breast cancer MCF-7 cells. Exp Cell Res 2002;281:115–127.

    Article  PubMed  CAS  Google Scholar 

  179. Sukocheva OA, Wang L, Albanese N, Pitson SM, Vadas MA, Xia P. Sphingosine kinase transmits estrogen signaling in human breast cancer cells. Mol Endocrinol 2003;17:2002–2012.

    Article  PubMed  CAS  Google Scholar 

  180. Jendiroba DB, Klostergaard J, Keyhani A, Pagliaro L, Freireich EJ. Effective cytotoxicity against human leukemias and chemotherapy-resistant leukemia cell lines by N-Ndimethylsphingosine. Leuk Res 2002;26:301–310.

    Article  PubMed  CAS  Google Scholar 

  181. Schwartz GK, Ward D, Saltz L, et al. A pilot clinical/pharmacological study of the protein kinase C-specific inhibitor safingol alone and in combination with doxorubicin. Clin Cancer Res 1997;3:537–543.

    PubMed  CAS  Google Scholar 

  182. Endo K, Igarashi Y, Nisar M, Zhou QH, Hakomori S. 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 1991;51:1613–1618.

    PubMed  CAS  Google Scholar 

  183. French KJ, Schrecengost RS, Lee BD, et al. Discovery and evaluation of inhibitors of human sphingosine kinase. Cancer Res 2003;63:5962–5969.

    PubMed  CAS  Google Scholar 

  184. Risau W. Mechanisms of angiogenesis. Nature 1997;386:671–674.

    Article  PubMed  CAS  Google Scholar 

  185. Chae SS, Paik JH, Furneaux H, Hla T. Requirement for sphingosine 1-phosphate receptor-1 in tumor angiogenesis demonstrated by in vivo RNA interference. J Clin Invest 2004;114:1082–1089.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biochemistry, Medical College of Virginia, Virginia Commonwealth School of Medicine, Richmond, VA

    Xianjun Fang & Sarah Spiegel

Authors
  1. Xianjun Fang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sarah Spiegel
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Biochemistry, University of Texas Health Center at Tyler, Tyler, TX

    Rakesh Srivastava

Rights and permissions

Reprints and permissions

Copyright information

© 2007 Humana Press Inc., Totowa, NJ

About this chapter

Cite this chapter

Fang, X., Spiegel, S. (2007). Role of Lysophospholipids in Cell Growth and Survival. In: Srivastava, R. (eds) Apoptosis, Cell Signaling, and Human Diseases. Humana Press. https://doi.org/10.1007/978-1-59745-200-7_7

Download citation

Publish with us

Policies and ethics

Search

Navigation