Gene Symbol: Sgpl1
Description: sphingosine phosphate lyase 1
Alias: AI428538, D10Xrf456, S1PL, Spl, sphingosine-1-phosphate lyase 1, SP-lyase 1, SPL 1, sphingosine-1-phosphate aldolase
Species: mouse
Products:     Sgpl1

Top Publications

  1. Schwab S, Pereira J, Matloubian M, Xu Y, Huang Y, Cyster J. Lymphocyte sequestration through S1P lyase inhibition and disruption of S1P gradients. Science. 2005;309:1735-9 pubmed
    ..We conclude that lymphocyte egress is mediated by S1P gradients that are established by S1P lyase activity and that the lyase may represent a novel immunosuppressant drug target. ..
  2. Hagen N, Van Veldhoven P, Proia R, Park H, Merrill A, van Echten Deckert G. Subcellular origin of sphingosine 1-phosphate is essential for its toxic effect in lyase-deficient neurons. J Biol Chem. 2009;284:11346-53 pubmed publisher
    ..In this model, S1P accumulated due to a defective lyase, however, this cause of toxicity might also be important in other cases, as illustrated by the neurotoxicity of cis-4-methylsphingosine phosphate. ..
  3. Allende M, Bektas M, Lee B, Bonifacino E, Kang J, Tuymetova G, et al. Sphingosine-1-phosphate lyase deficiency produces a pro-inflammatory response while impairing neutrophil trafficking. J Biol Chem. 2011;286:7348-58 pubmed publisher
    ..Thus, a genetic block in S1P degradation elicits a pro-inflammatory response but impairs neutrophil migration from blood into tissues. ..
  4. Ikeda M, Kihara A, Igarashi Y. Sphingosine-1-phosphate lyase SPL is an endoplasmic reticulum-resident, integral membrane protein with the pyridoxal 5'-phosphate binding domain exposed to the cytosol. Biochem Biophys Res Commun. 2004;325:338-43 pubmed
    ..S1P is degraded either by S1P lyase or by S1P phosphohydrolase. The gene encoding mammalian S1P lyase, SPL, has been identified. Here, we characterize the SPL protein in its expression, localization, and topology...
  5. Bektas M, Allende M, Lee B, Chen W, Amar M, Remaley A, et al. Sphingosine 1-phosphate lyase deficiency disrupts lipid homeostasis in liver. J Biol Chem. 2010;285:10880-9 pubmed publisher
    ..The disturbance of lipid homeostasis by altered sphingolipid levels may be relevant to metabolic diseases. ..
  6. Colié S, Van Veldhoven P, Kedjouar B, Bedia C, Albinet V, Sorli S, et al. Disruption of sphingosine 1-phosphate lyase confers resistance to chemotherapy and promotes oncogenesis through Bcl-2/Bcl-xL upregulation. Cancer Res. 2009;69:9346-53 pubmed publisher
    ..Irreversible degradation of S1P is catalyzed by S1P lyase (SPL). The human SGPL1 gene that encodes SPL maps to a region often mutated in cancers...
  7. Weber C, Krueger A, Münk A, Bode C, Van Veldhoven P, Gräler M. Discontinued postnatal thymocyte development in sphingosine 1-phosphate-lyase-deficient mice. J Immunol. 2009;183:4292-301 pubmed publisher
    ..S1P-lyase 1 (SGPL1) deficiency leads to accumulation of S1P in lymphoid tissues, which blocks lymphocyte egress and induces thymus ..
  8. Bandhuvula P, Honbo N, Wang G, Jin Z, Fyrst H, Zhang M, et al. S1P lyase: a novel therapeutic target for ischemia-reperfusion injury of the heart. Am J Physiol Heart Circ Physiol. 2011;300:H1753-61 pubmed publisher
    ..S1P lyase (SPL) is a stress-activated enzyme responsible for irreversible S1P catabolism...
  9. Vogel P, Donoviel M, Read R, Hansen G, Hazlewood J, Anderson S, et al. Incomplete inhibition of sphingosine 1-phosphate lyase modulates immune system function yet prevents early lethality and non-lymphoid lesions. PLoS ONE. 2009;4:e4112 pubmed publisher
    b>S1PL is an aldehyde-lyase that irreversibly cleaves sphingosine 1-phosphate (S1P) in the terminal step of sphingolipid catabolism...

More Information


  1. Zhao Y, Gorshkova I, Berdyshev E, He D, Fu P, Ma W, et al. Protection of LPS-induced murine acute lung injury by sphingosine-1-phosphate lyase suppression. Am J Respir Cell Mol Biol. 2011;45:426-35 pubmed publisher
    ..levels are tightly regulated by synthesis and degradation, we tested the hypothesis that inhibition of S1P lyase (S1PL), the enzyme that irreversibly degrades S1P via cleavage, could ameliorate ALI...
  2. Oskouian B, Sooriyakumaran P, Borowsky A, Crans A, Dillard Telm L, Tam Y, et al. Sphingosine-1-phosphate lyase potentiates apoptosis via p53- and p38-dependent pathways and is down-regulated in colon cancer. Proc Natl Acad Sci U S A. 2006;103:17384-9 pubmed
    ..S1P is irreversibly degraded by the enzyme S1P lyase (SPL). In this study, we show a crucial role for SPL in mediating cellular responses to stress...
  3. Schmahl J, Raymond C, Soriano P. PDGF signaling specificity is mediated through multiple immediate early genes. Nat Genet. 2007;39:52-60 pubmed
    ..We conclude that these genes form a network that controls specific processes downstream of PDGF signaling. ..
  4. Olivera A, Kitamura Y, Wright L, Allende M, Chen W, Kaneko Goto T, et al. Sphingosine-1-phosphate can promote mast cell hyper-reactivity through regulation of contactin-4 expression. J Leukoc Biol. 2013;94:1013-24 pubmed publisher
    ..Our findings argue that dysregulation in the metabolism of S1P is a contributing factor in modulating MC responsiveness and the allergic response. ..
  5. Degagné E, Pandurangan A, Bandhuvula P, Kumar A, Eltanawy A, Zhang M, et al. Sphingosine-1-phosphate lyase downregulation promotes colon carcinogenesis through STAT3-activated microRNAs. J Clin Invest. 2014;124:5368-84 pubmed publisher
    ..We generated mice with intestinal epithelium-specific Sgpl1 deletion and chemically induced colitis and tumor formation in these animals...
  6. Zhou J, Saba J. Identification of the first mammalian sphingosine phosphate lyase gene and its functional expression in yeast. Biochem Biophys Res Commun. 1998;242:502-7 pubmed
    ..Sphingosine-1-phosphate lyase (SPL) catalyzes the breakdown of S-1-P. Using the C...
  7. Kumar A, Oskouian B, Fyrst H, Zhang M, Paris F, Saba J. S1P lyase regulates DNA damage responses through a novel sphingolipid feedback mechanism. Cell Death Dis. 2011;2:e119 pubmed publisher
    ..S1P lyase (SPL) catalyzes the irreversible degradation of S1P in the final step of sphingolipid metabolism...
  8. Mezzar S, De Schryver E, Van Veldhoven P. RP-HPLC-fluorescence analysis of aliphatic aldehydes: application to aldehyde-generating enzymes HACL1 and SGPL1. J Lipid Res. 2014;55:573-82 pubmed publisher
    ..steps of these processes are 2-hydroxyacyl-CoA lyase (HACL1) and sphingosine-1-phosphate lyase (SGPL1), respectively...
  9. Ihlefeld K, Claas R, Koch A, Pfeilschifter J, Meyer Zu Heringdorf D. Evidence for a link between histone deacetylation and Ca²+ homoeostasis in sphingosine-1-phosphate lyase-deficient fibroblasts. Biochem J. 2012;447:457-64 pubmed publisher
    Embryonic fibroblasts from S1P (sphingosine-1-phosphate) lyase-deficient mice [Sgpl1-/- MEFs (mouse embryonic fibroblasts)] are characterized by intracellular accumulation of S1P, elevated cytosolic [Ca2+]i and enhanced Ca2+ storage...
  10. Newbigging S, Zhang M, Saba J. Immunohistochemical analysis of sphingosine phosphate lyase expression during murine development. Gene Expr Patterns. 2013;13:21-9 pubmed publisher
    Sphingosine-1-phosphate lyase (SPL) catalyzes the degradation of sphingosine-1-phosphate (S1P), a bioactive lipid that controls cell proliferation, migration and survival...
  11. Bot M, Van Veldhoven P, de Jager S, Johnson J, Nijstad N, Van Santbrink P, et al. Hematopoietic sphingosine 1-phosphate lyase deficiency decreases atherosclerotic lesion development in LDL-receptor deficient mice. PLoS ONE. 2013;8:e63360 pubmed publisher
    ..As S1P levels are tightly controlled by S1P lyase, we investigated the impact of hematopoietic S1P lyase (Sgpl1(-/-)) deficiency on leukocyte subsets relevant to atherosclerosis...
  12. Claas R, Ter Braak M, Hegen B, Hardel V, Angioni C, Schmidt H, et al. Enhanced Ca2+ storage in sphingosine-1-phosphate lyase-deficient fibroblasts. Cell Signal. 2010;22:476-83 pubmed publisher
    ..S1P metabolism thus plays a role not only in acute Ca2+ mobilization but also in long-term regulation of Ca2+ homeostasis. ..
  13. Ikeda M, Kihara A, Kariya Y, Lee Y, Igarashi Y. Sphingolipid-to-glycerophospholipid conversion in SPL-null cells implies the existence of an alternative isozyme. Biochem Biophys Res Commun. 2005;329:474-9 pubmed
    ..Until now, only one gene, SPL, has been identified as encoding a S1P lyase...
  14. Mendel J, Heinecke K, Fyrst H, Saba J. Sphingosine phosphate lyase expression is essential for normal development in Caenorhabditis elegans. J Biol Chem. 2003;278:22341-9 pubmed
    ..Our results show that sphingosine phosphate lyase is an essential gene in C. elegans and suggest that the sphingolipid degradative pathway plays a conserved role in regulating animal development. ..
  15. Ihlefeld K, Vienken H, Claas R, Blankenbach K, Rudowski A, Ter Braak M, et al. Upregulation of ABC transporters contributes to chemoresistance of sphingosine 1-phosphate lyase-deficient fibroblasts. J Lipid Res. 2015;56:60-9 pubmed publisher
    ..It has been reported previously that embryonic fibroblasts from S1P lyase-deficient mice (Sgpl1(-/-)-MEFs) are resistant to chemotherapy-induced apoptosis through upregulation of B cell lymphoma 2 (Bcl-2) and ..
  16. Abu Khweek A, Kanneganti A, Guttridge D D, Amer A. The Sphingosine-1-Phosphate Lyase (LegS2) Contributes to the Restriction of Legionella pneumophila in Murine Macrophages. PLoS ONE. 2016;11:e0146410 pubmed publisher
    ..It is homologous to the eukaryotic sphingosine lyase (SPL), an enzyme required in the terminal steps of sphingolipid metabolism...
  17. Maeda Y, Yagi H, Takemoto K, Utsumi H, Fukunari A, Sugahara K, et al. S1P lyase in thymic perivascular spaces promotes egress of mature thymocytes via up-regulation of S1P receptor 1. Int Immunol. 2014;26:245-55 pubmed publisher
    ..Our findings suggest that S1P lyase expressed in the thymic medullary PVS keeps the tissue S1P concentration low around the vessels and promotes thymic egress via up-regulation of S1P1. ..
  18. Harijith A, Pendyala S, Ebenezer D, Ha A, Fu P, Wang Y, et al. Hyperoxia-induced p47phox activation and ROS generation is mediated through S1P transporter Spns2, and S1P/S1P1&2 signaling axis in lung endothelium. Am J Physiol Lung Cell Mol Physiol. 2016;311:L337-51 pubmed publisher
    ..S1P is metabolized predominantly by S1P lyase and partial deletion of Sgpl1 (Sgpl1(+/-)) in mice accentuated lung injury...
  19. Brunkhorst R, Kanaan N, Koch A, Ferreirós N, Mirceska A, Zeiner P, et al. FTY720 treatment in the convalescence period improves functional recovery and reduces reactive astrogliosis in photothrombotic stroke. PLoS ONE. 2013;8:e70124 pubmed publisher
  20. Prasad R, Hadjidemetriou I, Maharaj A, Meimaridou E, Buonocore F, Saleem M, et al. Sphingosine-1-phosphate lyase mutations cause primary adrenal insufficiency and steroid-resistant nephrotic syndrome. J Clin Invest. 2017;127:942-953 pubmed publisher
    ..and steroid-resistant nephrotic syndrome caused by loss-of-function mutations in sphingosine-1-phosphate lyase (SGPL1)...
  21. Harijith A, Pendyala S, Reddy N, Bai T, Usatyuk P, Berdyshev E, et al. Sphingosine kinase 1 deficiency confers protection against hyperoxia-induced bronchopulmonary dysplasia in a murine model: role of S1P signaling and Nox proteins. Am J Pathol. 2013;183:1169-1182 pubmed publisher
    ..wild-type, sphingosine kinase1(-/-) (Sphk1(-/-)), sphingosine kinase 2(-/-) (Sphk2(-/-)), and S1P lyase(+/-) (Sgpl1(+/-)) mice were exposed to hyperoxia (75%) from postnatal day 1 to 7...
  22. Pirhaji L, Milani P, Dalin S, Wassie B, Dunn D, Fenster R, et al. Identifying therapeutic targets by combining transcriptional data with ordinal clinical measurements. Nat Commun. 2017;8:623 pubmed publisher
    ..sphingolipid metabolism in the disease and demonstrate that inhibiting the enzyme, sphingosine-1-phosphate lyase 1 (SPL), has neuroprotective effects in Huntington's disease models...
  23. Saba J, de la Garza Rodea A. S1P lyase in skeletal muscle regeneration and satellite cell activation: exposing the hidden lyase. Biochim Biophys Acta. 2013;1831:167-75 pubmed publisher
    ..S1P is irreversibly catabolized by S1P lyase (SPL), a highly conserved enzyme that catalyzes the cleavage of S1P at carbon bond C(2-3), resulting in formation of ..
  24. Borowsky A, Bandhuvula P, Kumar A, Yoshinaga Y, Nefedov M, Fong L, et al. Sphingosine-1-phosphate lyase expression in embryonic and adult murine tissues. J Lipid Res. 2012;53:1920-31 pubmed publisher
    ..S1P lyase (SPL) is the essential enzyme responsible for S1P degradation. SPL augments apoptosis and is down-regulated in cancer...
  25. Finney C, Hawkes C, Kain D, Dhabangi A, Musoke C, Cserti Gazdewich C, et al. S1P is associated with protection in human and experimental cerebral malaria. Mol Med. 2011;17:717-25 pubmed publisher
    ..These findings implicate dysregulation of the S1P pathway in the pathogenesis of human and murine CM and suggest a novel therapeutic strategy to improve clinical outcome in severe malaria. ..
  26. Schmahl J, Rizzolo K, Soriano P. The PDGF signaling pathway controls multiple steroid-producing lineages. Genes Dev. 2008;22:3255-67 pubmed publisher
    ..Therefore, PDGF signaling may constitute a common mechanism in the control of multiple steroidogenic lineages. ..
  27. Kirby R, Jin Y, Fu J, Cubillos J, Swertfeger D, Arend L. Dynamic regulation of sphingosine-1-phosphate homeostasis during development of mouse metanephric kidney. Am J Physiol Renal Physiol. 2009;296:F634-41 pubmed publisher
  28. Mitroi D, Karunakaran I, Gräler M, Saba J, Ehninger D, Ledesma M, et al. SGPL1 (sphingosine phosphate lyase 1) modulates neuronal autophagy via phosphatidylethanolamine production. Autophagy. 2017;13:885-899 pubmed publisher
    ..The roles of the bioactive signaling lipid sphingosine-1-phosphate (S1P) and its catabolic enzyme SGPL1/SPL (sphingosine phosphate lyase 1) in autophagy are increasingly recognized...
  29. Lovric S, Gonçalves S, Gee H, Oskouian B, Srinivas H, Choi W, et al. Mutations in sphingosine-1-phosphate lyase cause nephrosis with ichthyosis and adrenal insufficiency. J Clin Invest. 2017;127:912-928 pubmed publisher
    ..insufficiency, immunodeficiency, and neurological defects, we identified 9 different recessive mutations in SGPL1, which encodes sphingosine-1-phosphate (S1P) lyase...
  30. Peest U, Sensken S, Andréani P, Hänel P, Van Veldhoven P, Gräler M. S1P-lyase independent clearance of extracellular sphingosine 1-phosphate after dephosphorylation and cellular uptake. J Cell Biochem. 2008;104:756-72 pubmed publisher
    ..Our data thus show that extracellular S1P is dephosphorylated and subsequently converted by cells, which appears to be important for clearance of the signaling molecule S1P in the local tissue environment after infections or injuries. ..
  31. Billich A, Baumruker T, Beerli C, Bigaud M, Bruns C, Calzascia T, et al. Partial deficiency of sphingosine-1-phosphate lyase confers protection in experimental autoimmune encephalomyelitis. PLoS ONE. 2013;8:e59630 pubmed publisher
    ..regulates the egress of T cells from lymphoid organs; levels of S1P in the tissues are controlled by S1P lyase (Sgpl1). Hence, Sgpl1 offers a target to block T cell-dependent inflammatory processes...
  32. Ohtoyo M, Tamura M, Machinaga N, Muro F, Hashimoto R. Sphingosine 1-phosphate lyase inhibition by 2-acetyl-4-(tetrahydroxybutyl)imidazole (THI) under conditions of vitamin B6 deficiency. Mol Cell Biochem. 2015;400:125-33 pubmed publisher
    ..2-acetyl-4-(tetrahydroxybutyl)imidazole (THI) causes lymphopenia in animals through sphingosine 1-phosphate lyase (SPL) inhibition...
  33. Hagen N, Hans M, Hartmann D, Swandulla D, van Echten Deckert G. Sphingosine-1-phosphate links glycosphingolipid metabolism to neurodegeneration via a calpain-mediated mechanism. Cell Death Differ. 2011;18:1356-65 pubmed publisher
    ..We therefore propose that an impaired metabolism of glycosphingolipids, which are prevalent in the central nervous system, might be linked via S1P, their common catabolic intermediate, to neuronal death. ..
  34. de la Garza Rodea A, Baldwin D, Oskouian B, Place R, Bandhuvula P, Kumar A, et al. Sphingosine phosphate lyase regulates myogenic differentiation via S1P receptor-mediated effects on myogenic microRNA expression. FASEB J. 2014;28:506-19 pubmed publisher
    S1P lyase (SPL) catalyzes the irreversible degradation of sphingosine-1-phosphate (S1P), a bioactive lipid whose signaling activities regulate muscle differentiation, homeostasis, and satellite cell (SC) activation...
  35. Keller J, Catala Lehnen P, Huebner A, Jeschke A, Heckt T, Lueth A, et al. Calcitonin controls bone formation by inhibiting the release of sphingosine 1-phosphate from osteoclasts. Nat Commun. 2014;5:5215 pubmed publisher
    ..This study redefines the role of CT in skeletal biology, confirms that S1P acts as an osteoanabolic molecule in vivo and provides evidence for a pharmacologically exploitable crosstalk between osteoclasts and osteoblasts. ..
  36. Huang L, Berdyshev E, Tran J, Xie L, Chen J, Ebenezer D, et al. Sphingosine-1-phosphate lyase is an endogenous suppressor of pulmonary fibrosis: role of S1P signalling and autophagy. Thorax. 2015;70:1138-48 pubmed publisher
    ..the expression of S1PL in human lung fibroblasts via activation and binding of Smad3 transcription factor to Sgpl1 promoter...
  37. Karaca I, Tamboli I, Glebov K, Richter J, Fell L, Grimm M, et al. Deficiency of sphingosine-1-phosphate lyase impairs lysosomal metabolism of the amyloid precursor protein. J Biol Chem. 2014;289:16761-72 pubmed publisher
    ..Together, these data demonstrate that S1P-lyase plays a critical role in the regulation of lysosomal activity and the metabolism of APP. ..
  38. Hagen Euteneuer N, Lutjohann D, Park H, Merrill A, van Echten Deckert G. Sphingosine 1-phosphate (S1P) lyase deficiency increases sphingolipid formation via recycling at the expense of de novo biosynthesis in neurons. J Biol Chem. 2012;287:9128-36 pubmed publisher
    ..These changes, and their impact on the metabolism of other cellular lipids, should be explored as possible contributors to the neurodegeneration in S1P lyase deficiency. ..
  39. Ebenezer D, Fu P, Suryadevara V, Zhao Y, Natarajan V. Epigenetic regulation of pro-inflammatory cytokine secretion by sphingosine 1-phosphate (S1P) in acute lung injury: Role of S1P lyase. Adv Biol Regul. 2017;63:156-166 pubmed publisher
  40. Zamora Pineda J, Kumar A, Suh J, Zhang M, Saba J. Dendritic cell sphingosine-1-phosphate lyase regulates thymic egress. J Exp Med. 2016;213:2773-2791 pubmed
    ..junction produce the S1P egress signal, whereas thymic parenchymal S1P levels are kept low through S1P lyase (SPL)-mediated metabolism...
  41. Kariya Y, Kihara A, Ikeda M, Kikuchi F, Nakamura S, Hashimoto S, et al. Products by the sphingosine kinase/sphingosine 1-phosphate (S1P) lyase pathway but not S1P stimulate mitogenesis. Genes Cells. 2005;10:605-15 pubmed
    ..several mouse F9 embryonic carcinoma cell lines varying in expression of the S1P-degrading enzyme, S1P lyase (SPL) and/or sphingosine kinase (SPHK1)...
  42. Li R, Ren M, Chen N, Luo M, Zhang Z, Wu J. Vitronectin increases vascular permeability by promoting VE-cadherin internalization at cell junctions. PLoS ONE. 2012;7:e37195 pubmed publisher
    ..These results have important implications for the regulation of endothelial function and angiogenesis by VN under normal and pathological conditions. ..
  43. Kihara A, Ikeda M, Kariya Y, Lee E, Lee Y, Igarashi Y. Sphingosine-1-phosphate lyase is involved in the differentiation of F9 embryonal carcinoma cells to primitive endoderm. J Biol Chem. 2003;278:14578-85 pubmed
    Sphingosine 1-phosphate (S1P) is a bioactive lipid molecule that acts both extracellularly and intracellularly. The SPL gene encodes a mammalian S1P lyase that degrades S1P...