Sphingosine phosphate

Edg receptors are a group of recently discovered G-protein coupled receptors, which mediate the action of lysophospholipids (sphingosine-1 -phosphate, lysophosphatidic acid). Tachykinins and their Receptors... 

Lipid phosphate phosphohydrolases (LPPs), formerly called type 2 phosphatidate phosphohydrolases (PAP-2), catalyse the dephosphorylation of bioactive phospholipids (phosphatidic acid, ceramide-1-phosphate) and lysophospholipids (lysophosphatidic acid, sphingosine-1-phosphate). The substrate selectivity of individual LPPs is broad in contrast to the related sphingosine-1-phosphate phosphatase. LPPs are characterized by a lack of requirement for Mg2+ and insensitivity to N-ethylmaleimide. Three subtypes (LPP-1, LPP-2, LPP-3) have been identified in mammals. These enzymes have six putative transmembrane domains and three highly conserved domains that are characteristic of a phosphatase superfamily. Whether LPPs cleave extracellular mediators or rather have an influence on intracellular lipid phosphate concentrations is still a matter of debate. 

G-protein-coupled receptors (GPCRs), although some of them additionally play a role in intracellular signal transduction. Sphingosine-1-phosphate (SIP) and... 

Brinkmann V, Cyster JG, 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... 

Parrill AL, Sardar VM, Yuan H (2004) Sphingosine 1-phosphate and lysophosphatidic acid receptors agonist and antagonist binding and progress toward development of receptor-specific ligands. Semin Cell Dev Biol 15 467-476... 

Sphingosine kinases (SphKs) catalyse the phosphorylation of sphingosine to sphingosine-1 -phosphate (SIP). 

Most GPCRs interact with and activate more than one G-protein subfamily, e.g., with Gs plus Gq/n (histamine H2, parathyroid hormone and calcitonin recqrtors), Gs plus G (luteinising hormone receptor, 32-adrenoceptor) or Gq/11 plus G12/13 (thromboxane A2, angiotensin ATb endothelin ETA receptors). Some receptors show even broader G-protein coupling, e.g., to Gi, Gq/n plus Gi n ( protease-activated receptors, lysophosphatidate and sphingosine-1-phosphate receptors) or even to all four G-protein subfamilies (thyrotropin receptor). This multiple coupling results in multiple signaling via different pathways and in a concerted reaction of the cell to the stimulus. 

Chemokine and Sphingosine-1-phosphate Receptors in Tissue-Specific... 

Allende ML, Dreier JL, Mandala S, Proia RL. Expression of the sphingosine 1-phosphate receptor, S1P1, on T-cells controls thymic emigration. J Biol Chem 2004 279 15396-401. 

Bassi R, Anelli V, Giussani P, Tettamanti G, Viani P, Riboni L. Sphingosine-1-phosphate is released by cerebellar astrocytes in response to bFGF and induces astrocyte proliferation through G(i)-protein-coupled receptors. Glia 2006 53 621-630. 

Cinamon G, Matloubian M, Lesneski MJ, et al. Sphingosine 1-phosphate receptor 1 promotes B cell localization in the splenic marginal zone. Nat Immunol 2004 5 713-720. 

Graler MH, Goetzl EJ. The immunosuppressant FTY720 down-regulates sphingosine 1-phosphate G-protein-coupled receptors. FASEB J 2004 18(3) 551-553. 

Pyne S, Pyne NJ 2000 Sphingosine 1-phosphate signalling in mammalian cells. Biochem J 349 385M02... 

Sphingosine 1-Phosphate Type 1 Receptor Modulators Recent Advances and Therapeutic Potential... 

Auge, N., Nikolova-Karakashian, M., Carpentier, S., Parthasarathy, S., Negre-Salvayre, A., Salvayre, R., Merrill, A.H. Jr, Levade, T, 1999, Role of sphingosine 1-phosphate in the mitogenesis induced by oxidized LDL in smooth muscle cells via activation of sphingomyelinase, ceramidase, and sphingosine kinase, J. Biol. Chem. 274 21533-21538. 

Siess, W., Essler, M., and Brandi, R., 2000, Lysophosphatidic add and sphingosine 1-phosphate two hpid villains provoking cardiovascular diseases , lUBMB Life 49 167-171. 

Abbreviations CL, cardioUpin CDase, ceramidase Cer, Ceramide dhCer, dihydroceramide FBI, fumonisin Bl PA, phosphatidic acid PS, phosphatidylserine phytoCer, phytoceramide SPH, sphingosine SIP, sphingosine-1-phosphate. 

Spiegel, S., 1999, Sphingosine 1-phosphate a prototype of a new class of second messengers. J. Leukoc. Biol. 65 341-4. 

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