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Sphingosine 1-phosphate turnover

Sphingosine 1-phosphate turnover C

Contents

Overview
Subfamilies
Further reading
NC-IUPHAR subcommittee and family contributors
How to cite this family page

Overview

S1P (sphingosine 1-phosphate) is a pro-survival signal, in contrast to ceramide. It is formed by the sphingosine kinase-catalysed phosphorylation of sphingosine. S1P can be released from cells to act as an agonist at a family of five G protein-coupled receptors (S1P_1-5) but also has intracellular targets. S1P can be dephosphorylated back to sphingosine or hydrolysed to form hexadecanal and phosphoethanolamine. Sphingosine choline phosphotransferase (EC 2.7.8.10) generates sphingosylphosphocholine from sphingosine and CDP-choline. Sphingosine β-galactosyltransferase (EC 2.4.1.23) generates psychosine from sphingosine in the presence of UDP-α-D-galactose. The molecular identities of these enzymes have not been confirmed.

Subfamilies

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Further reading

* Key recommended reading is highlighted with an asterisk

Baker DL, Pham TC, Sparks MA. (2013) Structure and catalytic function of sphingosine kinases: analysis by site-directed mutagenesis and enzyme kinetics. Biochim. Biophys. Acta, 1831 (1): 139-46. [PMID:23000541]

Breiden B, Sandhoff K. (2014) The role of sphingolipid metabolism in cutaneous permeability barrier formation. Biochim. Biophys. Acta, 1841 (3): 441-52. [PMID:23954553]

* Chan H, Pitson SM. (2013) Post-translational regulation of sphingosine kinases. Biochim. Biophys. Acta, 1831 (1): 147-56. [PMID:22801036]

* Khavandgar Z, Murshed M. (2015) Sphingolipid metabolism and its role in the skeletal tissues. Cell. Mol. Life Sci., 72 (5): 959-69. [PMID:25424644]

Kihara A. (2014) Sphingosine 1-phosphate is a key metabolite linking sphingolipids to glycerophospholipids. Biochim. Biophys. Acta, 1841 (5): 766-72. [PMID:23994042]

Kunkel GT, Maceyka M, Milstien S, Spiegel S. (2013) Targeting the sphingosine-1-phosphate axis in cancer, inflammation and beyond. Nat Rev Drug Discov, 12 (9): 688-702. [PMID:23954895]

Le Stunff H, Peterson C, Thornton R, Milstien S, Mandala SM, Spiegel S. (2002) Characterization of murine sphingosine-1-phosphate phosphohydrolase. J. Biol. Chem., 277 (11): 8920-7. [PMID:11756451]

* Maceyka M, Spiegel S. (2014) Sphingolipid metabolites in inflammatory disease. Nature, 510 (7503): 58-67. [PMID:24899305]

Ogawa C, Kihara A, Gokoh M, Igarashi Y. (2003) Identification and characterization of a novel human sphingosine-1-phosphate phosphohydrolase, hSPP2. J. Biol. Chem., 278 (2): 1268-72. [PMID:12411432]

Orr Gandy KA, Obeid LM. (2013) Targeting the sphingosine kinase/sphingosine 1-phosphate pathway in disease: review of sphingosine kinase inhibitors. Biochim. Biophys. Acta, 1831 (1): 157-66. [PMID:22801037]

* Plano D, Amin S, Sharma AK. (2014) Importance of sphingosine kinase (SphK) as a target in developing cancer therapeutics and recent developments in the synthesis of novel SphK inhibitors. J. Med. Chem., 57 (13): 5509-24. [PMID:24471412]

Prager B, Spampinato SF, Ransohoff RM. (2015) Sphingosine 1-phosphate signaling at the blood-brain barrier. Trends Mol Med, 21 (6): 354-63. [PMID:25939882]

Proia RL, Hla T. (2015) Emerging biology of sphingosine-1-phosphate: its role in pathogenesis and therapy. J. Clin. Invest., 125 (4): 1379-87. [PMID:25831442]

Pyne NJ, Pyne S. (2010) Sphingosine 1-phosphate and cancer. Nat. Rev. Cancer, 10 (7): 489-503. [PMID:20555359]

* Pyne S, Pyne NJ. (2011) Translational aspects of sphingosine 1-phosphate biology. Trends Mol Med, 17 (8): 463-72. [PMID:21514226]

* Rosen H, Stevens RC, Hanson M, Roberts E, Oldstone MB. (2013) Sphingosine-1-phosphate and its receptors: structure, signaling, and influence. Annu. Rev. Biochem., 82: 637-62. [PMID:23527695]

Saba JD, de la Garza-Rodea AS. (2013) S1P lyase in skeletal muscle regeneration and satellite cell activation: exposing the hidden lyase. Biochim. Biophys. Acta, 1831 (1): 167-75. [PMID:22750505]

Sabourdy F, Astudillo L, Colacios C, Dubot P, Mrad M, Ségui B, Andrieu-Abadie N, Levade T. (2015) Monogenic neurological disorders of sphingolipid metabolism. Biochim. Biophys. Acta, 1851 (8): 1040-51. [PMID:25660725]

Schwalm S, Pfeilschifter J, Huwiler A. (2013) Sphingosine-1-phosphate: a Janus-faced mediator of fibrotic diseases. Biochim. Biophys. Acta, 1831 (1): 239-50. [PMID:22889995]

* Schwalm S, Pfeilschifter J, Huwiler A. (2014) Targeting the sphingosine kinase/sphingosine 1-phosphate pathway to treat chronic inflammatory kidney diseases. Basic Clin. Pharmacol. Toxicol., 114 (1): 44-9. [PMID:23789924]

Schwarzmann G, Arenz C, Sandhoff K. (2014) Labeled chemical biology tools for investigating sphingolipid metabolism, trafficking and interaction with lipids and proteins. Biochim. Biophys. Acta, 1841 (8): 1161-73. [PMID:24389251]

Zhang Y, Wang Y, Wan Z, Liu S, Cao Y, Zeng Z. (2014) Sphingosine kinase 1 and cancer: a systematic review and meta-analysis. PLoS ONE, 9 (2): e90362. [PMID:24587339]

NC-IUPHAR subcommittee and family contributors

How to cite this family page

Database page citation:

Susan Pyne. Sphingosine 1-phosphate turnover. Accessed on 12/07/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=776.

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Fabbro D, Kelly E, Marrion N, Peters JA, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Southan C, Davies JA and CGTP Collaborators (2015) The Concise Guide to PHARMACOLOGY 2015/16: Enzymes. Br J Pharmacol. 172: 6024-6109.