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a Departments of Medicine and Microbiology-Immunology, University of California Medical Center, San Francisco, California 94143–0711, USA
ABSTRACT
The lysophospholipid (LPL) mediators lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) are generated by enzymatic cleavage of stores of glycerophospholipids and sphingomyelin, respectively, in membranes of stimulated cells. LPLs are albumin bound, distributed widely in mammalian tissues, and increased in concentration by physiological activation of platelets and some other cells, tissue injury, inflammation, and neoplasia. The principal effects of LPA and S1P are growth related, including induction of cellular proliferation, alterations in differentiation and survival, and suppression of apoptosis. LPA and S1P also evoke cellular effector functions, which are dependent on cytoskeletal responses such as contraction, secretion, adhesion, and chemotaxis. The extracellular mediator activities of LPLs are transduced by subfamilies of G-protein-coupled receptors (GPCRs), of which the most completely characterized are those encoded by the endothelial differentiation genes (edgs). One homology cluster composed of Edg-1, -3, and -5 recognizes and responds to S1P, and the other cluster of Edg-2 and -4 is dedicated to LPA. Edg proteins are developmentally regulated and differ in tissue distribution, but couple similarly to multiple types of G-proteins to signal through ras and mitogen-activated protein kinase, rho, phospholipase C, and several protein tyrosine kinases. Numerous interactions between glycerophospholipids and sphingolipids are observed in their biosynthetic and signaling pathways. Many of the cellular effects of LPA and S1P are attributable to modifications in the content and/or activity of a major functional protein. Examples are increases in nuclear levels of transcription factors that regulate the serum response element, suppression of death caspase activities in apoptosis, and elevation of membrane content of heparin binding–epidermal growth factor-like growth factor, which serves as an autocrine and juxtacrine stimulus of proliferation. These ubiquitous LPL mediators of cellular growth, differentiation, and activities thus act directly through complex subfamilies of GPCRs and by regulating expression of biologically critical proteins.—Goetzl, E. J., An, S. Diversity of cellular receptors and functions for the lysophospholipid growth factors lysophosphatidic acid and sphingosine 1-phosphate. FASEB J. 12, 1589–1598 (1998)
Key Words: lysoglycerophospholipids • lysosphingophospholipids • G-protein-coupled receptors • signal transduction • apoptosis
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W. B. Thoreson, J. S. Ryan, C. Shi, M. E. Kelly, E. J. Bryson, M. L. Toews, T. L. Ediger, and D. M. Chacko Lysophosphatidic Acid Receptor Signaling in Mammalian Retinal Pigment Epithelial Cells Invest. Ophthalmol. Vis. Sci., July 1, 2002; 43(7): 2450 - 2461. [Abstract] [Full Text] [PDF]
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S. Gesta, M.-F. Simon, A. Rey, D. Sibrac, A. Girard, M. Lafontan, P. Valet, and J. S. Saulnier-Blache Secretion of a lysophospholipase D activity by adipocytes: involvement in lysophosphatidic acid synthesis J. Lipid Res., June 1, 2002; 43(6): 904 - 910. [Abstract] [Full Text] [PDF]
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I. Gennero, J. Fauvel, M. Nieto, C. Cariven, F. Gaits, F. Briand-Mesange, H. Chap, and J. P. Salles Apoptotic Effect of Sphingosine 1-Phosphate and Increased Sphingosine 1-Phosphate Hydrolysis on Mesangial Cells Cultured at Low Cell Density J. Biol. Chem., April 5, 2002; 277(15): 12724 - 12734. [Abstract] [Full Text] [PDF]
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 N. Hanafusa, Y. Yatomi, K. Yamada, Y. Hori, M. Nangaku, T. Okuda, T. Fujita, K. Kurokawa, and M. Fukagawa Sphingosine 1-phosphate stimulates rat mesangial cell proliferation from outside the cells Nephrol. Dial. Transplant., April 1, 2002; 17(4): 580 - 586. [Abstract] [Full Text] [PDF]
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L. T. Budnik and A. K. Mukhopadhyay Lysophosphatidic Acid and Its Role in Reproduction Biol Reprod, April 1, 2002; 66(4): 859 - 865. [Abstract] [Full Text] [PDF]
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J. Lu, Y.-j. Xiao, L. M. Baudhuin, G. Hong, and Y. Xu Role of ether-linked lysophosphatidic acids in ovarian cancer cells J. Lipid Res., March 1, 2002; 43(3): 463 - 476. [Abstract] [Full Text] [PDF]
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K. R. Watterson, E. Johnston, C. Chalmers, A. Pronin, S. J. Cook, J. L. Benovic, and T. M. Palmer Dual Regulation of EDG1/S1P1 Receptor Phosphorylation and Internalization by Protein Kinase C and G-protein-coupled Receptor Kinase 2 J. Biol. Chem., February 15, 2002; 277(8): 5767 - 5777. [Abstract] [Full Text] [PDF]
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A. Tokumura, Y. Kanaya, M. Kitahara, M. Miyake, Y. Yoshioka, and K. Fukuzawa Increased formation of lysophosphatidic acids by lysophospholipase D in serum of hypercholesterolemic rabbits J. Lipid Res., February 1, 2002; 43(2): 307 - 315. [Abstract] [Full Text] [PDF]
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 M. Tosaka, F. Okajima, Y. Hashiba, N. Saito, T. Nagano, T. Watanabe, T. Kimura, and T. Sasaki Sphingosine 1-Phosphate Contracts Canine Basilar Arteries In Vitro and In Vivo: Possible Role in Pathogenesis of Cerebral Vasospasm Stroke, December 1, 2001; 32(12): 2913 - 2919. [Abstract] [Full Text] [PDF]
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Y. Y. Sautin, J. M. Crawford, and S. I. Svetlov 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, December 1, 2001; 281(6): C2010 - C2019. [Abstract] [Full Text] [PDF]
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 T. Hla, M.-J. Lee, N. Ancellin, J. H. Paik, and M. J. Kluk Lysophospholipids--Receptor Revelations Science, November 30, 2001; 294(5548): 1875 - 1878. [Abstract] [Full Text] [PDF]
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 J. A. Koehler and M. F. Moran Regulation of Extracellular Signal-regulated Kinase Activity by p120 RasGAP Does Not Involve Its Pleckstrin Homology or Calcium-dependent Lipid Binding Domains but Does Require These Domains to Regulate Cell Proliferation Cell Growth Differ., November 1, 2001; 12(11): 551 - 561. [Abstract] [Full Text] [PDF]
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J. P. Gainor, C. A. Morton, J. T. Roberts, P. A. Vincent, and F. L. Minnear Platelet-conditioned medium increases endothelial electrical resistance independently of cAMP/PKA and cGMP/PKG Am J Physiol Heart Circ Physiol, November 1, 2001; 281(5): H1992 - H2001. [Abstract] [Full Text] [PDF]
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G. K. Marathe, A. R. Silva, H. C. de Castro Faria Neto, L. W. Tjoelker, S. M. Prescott, G. A. Zimmerman, and T. M. McIntyre Lysophosphatidylcholine and lyso-PAF display PAF-like activity derived from contaminating phospholipids J. Lipid Res., September 1, 2001; 42(9): 1430 - 1437. [Abstract] [Full Text] [PDF]
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 J. HEUSINGER-RIBEIRO, M. EBERLEIN, N. A. WAHAB, and M. GOPPELT-STRUEBE Expression of Connective Tissue Growth Factor in Human Renal Fibroblasts: Regulatory Roles of RhoA and cAMP J. Am. Soc. Nephrol., September 1, 2001; 12(9): 1853 - 1861. [Abstract] [Full Text] [PDF]
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L. T. Budnik and A. K. Mukhopadhyay Lysophosphatidic Acid Antagonizes the Morphoregulatory Effects of the Luteinizing Hormone on Luteal Cells: Possible Role of Small Rho-G-Proteins Biol Reprod, July 1, 2001; 65(1): 180 - 187. [Abstract] [Full Text] [PDF]
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 O. E. Olorundare, O. Peyruchaud, R. M. Albrecht, and D. F. Mosher Assembly of a fibronectin matrix by adherent platelets stimulated by lysophosphatidic acid and other agonists Blood, July 1, 2001; 98(1): 117 - 124. [Abstract] [Full Text] [PDF]
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 F. Liu, A. D. Verin, P. Wang, R. Day, R. P. Wersto, F. J. Chrest, D. K. English, and J. G. N. Garcia Differential Regulation of Sphingosine-1-Phosphate- and VEGF-Induced Endothelial Cell Chemotaxis . Involvement of Gialpha 2-Linked Rho Kinase Activity Am. J. Respir. Cell Mol. Biol., June 1, 2001; 24(6): 711 - 719. [Abstract] [Full Text] [PDF]
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 M Goppelt-Struebe, A Hahn, D Iwanciw, M Rehm, and B Banas Regulation of connective tissue growth factor (ccn2; ctgf) gene expression in human mesangial cells: modulation by HMG CoA reductase inhibitors (statins) Mol. Pathol., June 1, 2001; 54(3): 176 - 179. [Abstract] [Full Text]
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Y.-L. Hu, M.-K. Tee, E. J. Goetzl, N. Auersperg, G. B. Mills, N. Ferrara, and R. B. Jaffe Lysophosphatidic Acid Induction of Vascular Endothelial Growth Factor Expression in Human Ovarian Cancer Cells J Natl Cancer Inst, May 16, 2001; 93(10): 762 - 767. [Abstract] [Full Text] [PDF]
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D. A. Fishman, Y. Liu, S. M. Ellerbroek, and M. S. Stack Lysophosphatidic Acid Promotes Matrix Metalloproteinase (MMP) Activation and MMP-dependent Invasion in Ovarian Cancer Cells Cancer Res., April 1, 2001; 61(7): 3194 - 3199. [Abstract] [Full Text]
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 H. Ohata, K.-i. Tanaka, N. Maeyama, M. Yamamoto, and K. Momose Visualization of elementary mechanosensitive Ca2+-influx events, Ca2+ spots, in bovine lens epithelial cells J. Physiol., April 1, 2001; 532(1): 31 - 42. [Abstract] [Full Text] [PDF]
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T. Chiu and E. Rozengurt PKD in intestinal epithelial cells: rapid activation by phorbol esters, LPA, and angiotensin through PKC Am J Physiol Cell Physiol, April 1, 2001; 280(4): C929 - C942. [Abstract] [Full Text] [PDF]
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 D. English, J. G.N. Garcia, and D.N. Brindley Platelet-released phospholipids link haemostasis and angiogenesis Cardiovasc Res, February 16, 2001; 49(3): 588 - 599. [Abstract] [Full Text] [PDF]
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Y. Zheng, Y. Kong, and E. J. Goetzl Lysophosphatidic Acid Receptor-Selective Effects on Jurkat T Cell Migration Through a Matrigel Model Basement Membrane J. Immunol., February 15, 2001; 166(4): 2317 - 2322. [Abstract] [Full Text] [PDF]
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L. Balazs, J. Okolicany, M. Ferrebee, B. Tolley, and G. Tigyi Topical application of the phospholipid growth factor lysophosphatidic acid promotes wound healing in vivo Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2001; 280(2): R466 - R472. [Abstract] [Full Text] [PDF]
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M Starz-Gaiano, N. Cho, A Forbes, and R Lehmann Spatially restricted activity of a Drosophila lipid phosphatase guides migrating germ cells Development, January 3, 2001; 128(6): 983 - 991. [Abstract] [PDF]
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 Y. Xu, Y.-j. Xiao, L. M. Baudhuin, and B. M. Schwartz The Role and Clinical Applications of Bioactive Lysolipids in Ovarian Cancer Reproductive Sciences, January 1, 2001; 8(1): 1 - 13. [Abstract] [PDF]
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J. S. Saulnier-Blache, A. Girard, M.-F. Simon, M. Lafontan, and P. Valet A simple and highly sensitive radioenzymatic assay for lysophosphatidic acid quantification J. Lipid Res., December 1, 2000; 41(12): 1947 - 1951. [Abstract] [Full Text]
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A. T. KOVALA, K. A. HARVEY, P. McGLYNN, G. BOGUSLAWSKI, J. G. N. GARCIA, and D. ENGLISH High-efficiency transient transfection of endothelial cells for functional analysis FASEB J, December 1, 2000; 14(15): 2486 - 2494. [Abstract] [Full Text]
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Y. Yatomi, T. Ohmori, G. Rile, F. Kazama, H. Okamoto, T. Sano, K. Satoh, S. Kume, G. Tigyi, Y. Igarashi, et al. Sphingosine 1-phosphate as a major bioactive lysophospholipid that is released from platelets and interacts with endothelial cells Blood, November 15, 2000; 96(10): 3431 - 3438. [Abstract] [Full Text] [PDF]
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M. Garbi, S. Rubinstein, Y. Lax, and H. Breitbart Activation of Protein Kinase C{alpha} in the Lysophosphatidic Acid-Induced Bovine Sperm Acrosome Reaction and Phospholipase D1 Regulation Biol Reprod, November 1, 2000; 63(5): 1271 - 1277. [Abstract] [Full Text]
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 T. L. Ediger and M. L. Toews Synergistic Stimulation of Airway Smooth Muscle Cell Mitogenesis J. Pharmacol. Exp. Ther., September 1, 2000; 294(3): 1076 - 1082. [Abstract] [Full Text]
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