Gene Symbol: Sphk1
Description: sphingosine kinase 1
Alias: 1110006G24Rik, Sk1, Spk1, sphingosine kinase 1
Species: mouse
Products:     Sphk1

Top Publications

  1. Ross J, Hu W, Rosen B, Snider A, Obeid L, Cowart L. Sphingosine kinase 1 is regulated by peroxisome proliferator-activated receptor ? in response to free fatty acids and is essential for skeletal muscle interleukin-6 production and signaling in diet-induced obesity. J Biol Chem. 2013;288:22193-206 pubmed publisher
    We previously demonstrated that sphingosine kinase 1 (Sphk1) expression and activity are up-regulated by exogenous palmitate (PAL) in a skeletal muscle model system and in diet-induced obesity in mice; however, potential functions and in ..
  2. Shirai K, Kaneshiro T, Wada M, Furuya H, Bielawski J, Hannun Y, et al. A role of sphingosine kinase 1 in head and neck carcinogenesis. Cancer Prev Res (Phila). 2011;4:454-62 pubmed publisher
    ..suggests that the bioactive sphingolipids, such as sphingosine-1-phosphate (S1P) and its generating enzyme, sphingosine kinase 1 (SphK1) play pivotal roles in several important biological functions including promoting tumor growth and ..
  3. Wu W, Mosteller R, Broek D. Sphingosine kinase protects lipopolysaccharide-activated macrophages from apoptosis. Mol Cell Biol. 2004;24:7359-69 pubmed
    ..7 cells resulted in a time- and dose-dependent activation of SPK and membrane translocation of SPK1. Further, LPS-induced SPK activation was blocked by SPK1-specific small interfering RNA (siRNA)...
  4. Zemann B, Urtz N, Reuschel R, Mechtcheriakova D, Bornancin F, Badegruber R, et al. Normal neutrophil functions in sphingosine kinase type 1 and 2 knockout mice. Immunol Lett. 2007;109:56-63 pubmed
    ..An in vivo model of bacterial lung infection revealed an accelerated progression of disease in SPHK2 (but not SPHK1) knockout mice as compared to wild-type controls...
  5. Liu H, Sugiura M, Nava V, Edsall L, Kono K, Poulton S, et al. Molecular cloning and functional characterization of a novel mammalian sphingosine kinase type 2 isoform. J Biol Chem. 2000;275:19513-20 pubmed
    ..Based on sequence homology to murine and human sphingosine kinase-1 (SPHK1), which we recently cloned (Kohama, T., Oliver, A., Edsall, L. , Nagiec, M. M., Dickson, R., and Spiegel, S...
  6. Kanno T, Nishizaki T, Proia R, Kajimoto T, Jahangeer S, Okada T, et al. Regulation of synaptic strength by sphingosine 1-phosphate in the hippocampus. Neuroscience. 2010;171:973-80 pubmed publisher
    ..LTP was impaired in hippocampal slices specifically in the CA3 region obtained from SphK1-knockout mice, which correlates well with the poor performance of these animals in the Morris water maze test...
  7. Di A, Kawamura T, Gao X, Tang H, Berdyshev E, Vogel S, et al. A novel function of sphingosine kinase 1 suppression of JNK activity in preventing inflammation and injury. J Biol Chem. 2010;285:15848-57 pubmed publisher
    The mechanism underlying the protective effect of sphingosine kinase 1 (SphK1) in inflammatory injury is not clear...
  8. Gellings Lowe N, Swaney J, Moreno K, Sabbadini R. Sphingosine-1-phosphate and sphingosine kinase are critical for transforming growth factor-beta-stimulated collagen production by cardiac fibroblasts. Cardiovasc Res. 2009;82:303-12 pubmed publisher
    ..TGF-beta increased sphingosine kinase 1 (SphK1; the enzyme responsible for S1P production) expression and activity...
  9. Lai W, Goh H, Bao Z, Wong W, Melendez A, Leung B. The role of sphingosine kinase in a murine model of allergic asthma. J Immunol. 2008;180:4323-9 pubmed
    ..bronchoalveolar lavage, IL-4, IL-5, eotaxin, and serum OVA-specific IgE levels was observed in mice with SphK1 knock-down via small interfering RNA approach...

More Information


  1. Venkataraman K, Thangada S, Michaud J, Oo M, Ai Y, Lee Y, et al. Extracellular export of sphingosine kinase-1a contributes to the vascular S1P gradient. Biochem J. 2006;397:461-71 pubmed
    ..Biol. Chem. 277, 6667-6675] that Sphk1 activity is constitutively secreted by vascular endothelial cells...
  2. Allende M, Sasaki T, Kawai H, Olivera A, Mi Y, van Echten Deckert G, et al. Mice deficient in sphingosine kinase 1 are rendered lymphopenic by FTY720. J Biol Chem. 2004;279:52487-92 pubmed
    ..Two such kinases have been identified, SPHK1 and SPHK2...
  3. Yang J, Castle B, Hanidu A, Stevens L, Yu Y, Li X, et al. Sphingosine kinase 1 is a negative regulator of CD4+ Th1 cells. J Immunol. 2005;175:6580-8 pubmed
    ..In this study we report that sphingosine kinase 1 (SPHK1), but not SPHK2, is highly expressed in DO11.10 Th1 cells...
  4. Hammad S, Crellin H, Wu B, Melton J, Anelli V, Obeid L. Dual and distinct roles for sphingosine kinase 1 and sphingosine 1 phosphate in the response to inflammatory stimuli in RAW macrophages. Prostaglandins Other Lipid Mediat. 2008;85:107-14 pubmed publisher
    b>Sphingosine kinase 1 (SK1) and its product sphingosine-1-phosphate (S1P) have been implicated in the regulation of many cellular processes including growth regulation, protection from apoptosis, stimulation of angiogenesis, and most ..
  5. Kohno M, Momoi M, Oo M, Paik J, Lee Y, Venkataraman K, et al. Intracellular role for sphingosine kinase 1 in intestinal adenoma cell proliferation. Mol Cell Biol. 2006;26:7211-23 pubmed
    ..Here, we show that Sphk1 is expressed and is required for small intestinal tumor cell proliferation in Apc Min/+ mice...
  6. Kusner D, Thompson C, Melrose N, Pitson S, Obeid L, Iyer S. The localization and activity of sphingosine kinase 1 are coordinately regulated with actin cytoskeletal dynamics in macrophages. J Biol Chem. 2007;282:23147-62 pubmed
    ..We tested the hypothesis that interactions with actin filaments regulate the localization of SK1 to membrane surfaces, including the plasma membrane and phagosome...
  7. Lai W, Irwan A, Goh H, Melendez A, McInnes I, Leung B. Distinct roles of sphingosine kinase 1 and 2 in murine collagen-induced arthritis. J Immunol. 2009;183:2097-103 pubmed publisher
    ..To date, two mammalian isoenzymes, SphK1 and SphK2, have been identified...
  8. Heffernan Stroud L, Helke K, Jenkins R, de Costa A, Hannun Y, Obeid L. Defining a role for sphingosine kinase 1 in p53-dependent tumors. Oncogene. 2012;31:1166-75 pubmed publisher
    ..In this study, we demonstrate that the enzyme sphingosine kinase 1 (SK1), a critical enzyme in the regulation of the key bioactive sphingolipids ceramide, sphingosine and ..
  9. Nayak D, Huo Y, Kwang W, Pushparaj P, Kumar S, Ling E, et al. Sphingosine kinase 1 regulates the expression of proinflammatory cytokines and nitric oxide in activated microglia. Neuroscience. 2010;166:132-44 pubmed publisher
    ..In this study, we demonstrate that sphingosine kinase1 (SphK1), a key enzyme of the sphingolipid metabolic pathway, and its receptors are expressed in the mouse BV2 microglial ..
  10. Kawamori T, Kaneshiro T, Okumura M, Maalouf S, Uflacker A, Bielawski J, et al. Role for sphingosine kinase 1 in colon carcinogenesis. FASEB J. 2009;23:405-14 pubmed publisher
    b>Sphingosine kinase 1 (SphK1) phosphorylates sphingosine to form sphingosine-1-phosphate (S1P) and is a critical regulator of sphingolipid-mediated functions. Cell-based studies suggest a tumor-promoting function for the SphK1/S1P pathway...
  11. Fukuda Y, Kihara A, Igarashi Y. Distribution of sphingosine kinase activity in mouse tissues: contribution of SPHK1. Biochem Biophys Res Commun. 2003;309:155-60 pubmed
    ..Thus far, two sphingosine kinases have been reported, with SPHK1 exhibiting the higher activity. However, several studies suggest the existence of unidentified sphingosine kinases...
  12. Niessen F, Schaffner F, Furlan Freguia C, Pawlinski R, Bhattacharjee G, Chun J, et al. Dendritic cell PAR1-S1P3 signalling couples coagulation and inflammation. Nature. 2008;452:654-8 pubmed publisher
    ..Thus, activation of dendritic cells by coagulation in the lymphatics emerges as a previously unknown mechanism that promotes systemic inflammation and lethality in decompensated innate immune responses. ..
  13. Mizugishi K, Yamashita T, Olivera A, Miller G, Spiegel S, Proia R. Essential role for sphingosine kinases in neural and vascular development. Mol Cell Biol. 2005;25:11113-21 pubmed
    ..Our findings also suggest that exploitation of this potent neuronal survival pathway could lead to the development of novel therapeutic approaches for neurological diseases. ..
  14. Park S, Kim M, Kim M, D Agati V, Lee H. Sphingosine kinase 1 protects against renal ischemia-reperfusion injury in mice by sphingosine-1-phosphate1 receptor activation. Kidney Int. 2011;80:1315-27 pubmed publisher
    The roles of sphingosine kinases SK1 and SK2 in ischemia-reperfusion injury have not been fully elucidated since studies have found beneficial effects of SK1 while others showed no role in this injury...
  15. Kawahara A, Nishi T, Hisano Y, Fukui H, Yamaguchi A, Mochizuki N. The sphingolipid transporter spns2 functions in migration of zebrafish myocardial precursors. Science. 2009;323:524-7 pubmed publisher
    ..Thus, Spns2 in the YSL functions as a S1P transporter in S1P secretion, thereby regulating myocardial precursor migration. ..
  16. Pham T, Baluk P, Xu Y, Grigorova I, Bankovich A, Pappu R, et al. Lymphatic endothelial cell sphingosine kinase activity is required for lymphocyte egress and lymphatic patterning. J Exp Med. 2010;207:17-27 pubmed publisher
    ..Our data provide evidence that lymphatic endothelial cells are an in vivo source of S1P required for lymphocyte egress from LNs and Peyer's patches, and suggest a role for S1P in lymphatic vessel maturation. ..
  17. Tauseef M, Kini V, Knezevic N, Brannan M, Ramchandaran R, Fyrst H, et al. Activation of sphingosine kinase-1 reverses the increase in lung vascular permeability through sphingosine-1-phosphate receptor signaling in endothelial cells. Circ Res. 2008;103:1164-72 pubmed publisher
    ..Here, we investigated the role of SPHK1 activation in regulating the increase in pulmonary microvessel permeability induced by challenge of mice with ..
  18. Meacci E, Nuti F, Donati C, Cencetti F, Farnararo M, Bruni P. Sphingosine kinase activity is required for myogenic differentiation of C2C12 myoblasts. J Cell Physiol. 2008;214:210-20 pubmed
    ..Indeed, SphK activity, SphK1 protein content and S1P formation were found to be enhanced in myoblasts that became confluent as well as in ..
  19. Kihara A, Anada Y, Igarashi Y. Mouse sphingosine kinase isoforms SPHK1a and SPHK1b differ in enzymatic traits including stability, localization, modification, and oligomerization. J Biol Chem. 2006;281:4532-9 pubmed
    ..Thus, although these two proteins differ only in a few N-terminal amino acid residues, their enzymatic traits are extremely different. ..
  20. Kim M, Kim M, Kim N, D Agati V, Emala C, Lee H. Isoflurane mediates protection from renal ischemia-reperfusion injury via sphingosine kinase and sphingosine-1-phosphate-dependent pathways. Am J Physiol Renal Physiol. 2007;293:F1827-35 pubmed
    ..In addition, mice deficient in SK1 enzyme were not protected from IR injury with isoflurane...
  21. Donati C, Cencetti F, De Palma C, Rapizzi E, Brunelli S, Cossu G, et al. TGFbeta protects mesoangioblasts from apoptosis via sphingosine kinase-1 regulation. Cell Signal. 2009;21:228-36 pubmed publisher
    ..TGFbeta exerts a marked anti-apoptotic action in mesoangioblasts with a mechanism involving regulation of sphingosine kinase 1 (SphK1), one of the isoforms responsible for S1P formation...
  22. Alvarez S, Harikumar K, Hait N, Allegood J, STRUB G, Kim E, et al. Sphingosine-1-phosphate is a missing cofactor for the E3 ubiquitin ligase TRAF2. Nature. 2010;465:1084-8 pubmed publisher
    ..TRAF2 binds to sphingosine kinase 1 (SphK1), one of the isoenzymes that generates the pro-survival lipid mediator sphingosine-1-phosphate (S1P) ..
  23. Kono Y, Nishiuma T, Nishimura Y, Kotani Y, Okada T, Nakamura S, et al. Sphingosine kinase 1 regulates differentiation of human and mouse lung fibroblasts mediated by TGF-beta1. Am J Respir Cell Mol Biol. 2007;37:395-404 pubmed
    ..We found, in a mouse model of bleomycin lung fibrosis, that SPHK1 and alpha-SMA were colocalized within lung fibrotic foci and that these expressions were significantly increased ..
  24. Michaud J, Kohno M, Proia R, Hla T. Normal acute and chronic inflammatory responses in sphingosine kinase 1 knockout mice. FEBS Lett. 2006;580:4607-12 pubmed
    ..Here we show that sphingosine kinase 1 knockout mice exhibit normal inflammatory cell recruitment during thioglycollate-induced peritonitis and ..
  25. Baker D, Barth J, Chang R, Obeid L, Gilkeson G. Genetic sphingosine kinase 1 deficiency significantly decreases synovial inflammation and joint erosions in murine TNF-alpha-induced arthritis. J Immunol. 2010;185:2570-9 pubmed publisher
    b>Sphingosine kinase 1 (SphK1) is an enzyme that converts sphingosine to bioactive sphingosine-1-phosphate. Recent in vitro data suggest a potential role of SphK1 in TNF-alpha-mediated inflammation...
  26. Pappu R, Schwab S, Cornelissen I, Pereira J, Regard J, Xu Y, et al. Promotion of lymphocyte egress into blood and lymph by distinct sources of sphingosine-1-phosphate. Science. 2007;316:295-8 pubmed
    ..Disruption of compartmentalized S1P signaling is a plausible mechanism by which S1P-receptor-1 agonists function as immunosuppressives. ..
  27. Yadav M, Clark L, Schorey J. Macrophage's proinflammatory response to a mycobacterial infection is dependent on sphingosine kinase-mediated activation of phosphatidylinositol phospholipase C, protein kinase C, ERK1/2, and phosphatidylinositol 3-kinase. J Immunol. 2006;176:5494-503 pubmed
    ..These studies are the first to show that the macrophage proinflammatory response following a mycobacterial infection is regulated by SPK/PI-PLC/PKC activation of ERK1/2 and PI3K pathways. ..
  28. Lai W, Irwan A, Goh H, Howe H, Yu D, Valle Oñate R, et al. Anti-inflammatory effects of sphingosine kinase modulation in inflammatory arthritis. J Immunol. 2008;181:8010-7 pubmed
    ..a potent SphK inhibitor, N,N-dimethylsphingosine (DMS), and a molecular approach against one of its isoenzymes, SphK1. We observed that levels of S1P in the synovial fluid of RA patients were significantly higher than those of ..
  29. Snider A, Kawamori T, Bradshaw S, Orr K, Gilkeson G, Hannun Y, et al. A role for sphingosine kinase 1 in dextran sulfate sodium-induced colitis. FASEB J. 2009;23:143-52 pubmed publisher
    ..S1P formation is catalyzed by sphingosine kinase (SK), of which the SK1 isoenzyme is activated by tumor necrosis alpha (TNF-alpha)...
  30. Wadgaonkar R, Patel V, Grinkina N, Romano C, Liu J, Zhao Y, et al. Differential regulation of sphingosine kinases 1 and 2 in lung injury. Am J Physiol Lung Cell Mol Physiol. 2009;296:L603-13 pubmed publisher
    Two mammalian sphingosine kinase (SphK) isoforms, SphK1 and SphK2, possess identical kinase domains but have distinct kinetic properties and subcellular localizations, suggesting each has one or more specific roles in sphingosine-1-..
  31. Kohama T, Olivera A, Edsall L, Nagiec M, Dickson R, Spiegel S. Molecular cloning and functional characterization of murine sphingosine kinase. J Biol Chem. 1998;273:23722-8 pubmed
    ..Our data suggest that sphingosine kinase is a prototypical member of a new class of lipid kinases. Cloning of sphingosine kinase is an important step in corroborating the intracellular role of SPP as a second messenger. ..
  32. Le Scolan E, Pchejetski D, Banno Y, Denis N, Mayeux P, Vainchenker W, et al. Overexpression of sphingosine kinase 1 is an oncogenic event in erythroleukemic progression. Blood. 2005;106:1808-16 pubmed
    ..The data show that transcriptional up-regulation of the sphingosine kinase gene (SPHK1) is a recurrent event associated with the tumorigenic phenotype of these transgenic proerythroblasts...
  33. Jo S, Bajwa A, Ye H, Vergis A, Awad A, Kharel Y, et al. Divergent roles of sphingosine kinases in kidney ischemia-reperfusion injury. Kidney Int. 2009;75:167-75 pubmed publisher
    Sphingosine-1-phosphate (S1P), produced by sphingosine kinase 1 (SphK1) or kinase 2 (SphK2), mediates biological effects through intracellular and/or extracellular mechanisms...
  34. Camerer E, Regard J, Cornelissen I, Srinivasan Y, Duong D, Palmer D, et al. Sphingosine-1-phosphate in the plasma compartment regulates basal and inflammation-induced vascular leak in mice. J Clin Invest. 2009;119:1871-9 pubmed
    ..Our results suggest that the blood communicates with blood vessels via plasma S1P to maintain vascular integrity and regulate vascular leak. This pathway prevents lethal responses to leak-inducing mediators in mouse models. ..
  35. 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
    ..These findings reveal how S1P can activate SCs and indicate that SPL suppression may provide a therapeutic strategy for myopathies. This article is part of a Special Issue entitled Advances in Lysophospholipid Research. ..
  36. Tao R, Zhang J, Vessey D, Honbo N, Karliner J. Deletion of the sphingosine kinase-1 gene influences cell fate during hypoxia and glucose deprivation in adult mouse cardiomyocytes. Cardiovasc Res. 2007;74:56-63 pubmed
    ..We tested the following hypotheses: 1] cardiac myocytes null for the SphK1 gene are more vulnerable to the stress of hypoxia+glucose deprivation; 2] the monoganglioside GM-1, which ..
  37. Gorshkova I, Wang H, Orbelyan G, Goya J, Natarajan V, Beiser D, et al. Inhibition of sphingosine-1-phosphate lyase rescues sphingosine kinase-1-knockout phenotype following murine cardiac arrest. Life Sci. 2013;93:359-66 pubmed publisher
    ..C57BL/6 and sphingosine kinase-1 knockout (SphK1-KO) female mice were arrested for 8 min then subjected to 5 minute CPR with epinephrine bolus given at 90s after ..
  38. Diesner S, Olivera A, Dillahunt S, Schultz C, Watzlawek T, Förster Waldl E, et al. Sphingosine-kinase 1 and 2 contribute to oral sensitization and effector phase in a mouse model of food allergy. Immunol Lett. 2012;141:210-9 pubmed publisher
    ..g.) administered ovalbumin (OVA) with concomitant acid-suppression. Wild-type (WT), SphK1(-/-) and SphK2(-/-) mice immunized with OVA alone i.g. or intraperitoneally (i.p...
  39. Vettorazzi S, Bode C, Dejager L, Frappart L, Shelest E, Klaßen C, et al. Glucocorticoids limit acute lung inflammation in concert with inflammatory stimuli by induction of SphK1. Nat Commun. 2015;6:7796 pubmed publisher
    ..Contrarily, synergistic gene induction of sphingosine kinase 1 (SphK1) by glucocorticoids and pro-inflammatory stimuli via the glucocorticoid receptor in macrophages ..
  40. Qi Y, Wang W, Chen J, Dai L, Kaczorowski D, Gao X, et al. Sphingosine Kinase 1 Protects Hepatocytes from Lipotoxicity via Down-regulation of IRE1α Protein Expression. J Biol Chem. 2015;290:23282-90 pubmed publisher
    ..This study demonstrates a pivotal role of sphingosine kinase 1 (SphK1) in protecting hepatocytes from lipotoxicity...
  41. Martin C, Lafosse J, Malavaud B, Cuvillier O. Sphingosine kinase-1 mediates androgen-induced osteoblast cell growth. Biochem Biophys Res Commun. 2010;391:669-73 pubmed publisher
    Herein we report that the lipid kinase sphingosine kinase-1 (SphK1) is instrumental in mediating androgen-induced cell proliferation in osteoblasts...
  42. Wendler C, Rivkees S. Sphingosine-1-phosphate inhibits cell migration and endothelial to mesenchymal cell transformation during cardiac development. Dev Biol. 2006;291:264-77 pubmed
    ..These data indicate that S1P, locally maintained within a specific concentration range, is an important and necessary component of early heart development. ..
  43. Terada N, Banno Y, Ohno N, Fujii Y, Murate T, Sarna J, et al. Compartmentation of the mouse cerebellar cortex by sphingosine kinase. J Comp Neurol. 2004;469:119-27 pubmed
    ..The selective expression of SPHK in the zebrin II-immunoreactive PCs may explain their resistance to cell death when ceramide metabolism is disrupted, as in the acid sphingomyelinase knockout model of Niemann-Pick type A/B disease. ..
  44. Yeh C, Li H, Malhotra D, Huang M, Zhu B, Goetzl E, et al. Sphingolipid signaling and treatment during remodeling of the uninfarcted ventricular wall after myocardial infarction. Am J Physiol Heart Circ Physiol. 2009;296:H1193-9 pubmed publisher
  45. Liu Y, Saiyan S, Men T, Gao H, Wen C, Liu Y, et al. Hepatopoietin Cn reduces ethanol-induced hepatoxicity via sphingosine kinase 1 and sphingosine 1-phosphate receptors. J Pathol. 2013;230:365-76 pubmed publisher
    ..study demonstrated that HPPCn attenuated oxidative injury and fibrosis induced by ethanol feeding and that the SphK1/S1P/S1PRs signalling pathway contributes to the protective effect of HPPCn on hepatocyte apoptosis and HSC ..
  46. Furuya H, Shimizu Y, Tamashiro P, Iino K, Bielawski J, Chan O, et al. Sphingosine kinase 1 expression enhances colon tumor growth. J Transl Med. 2017;15:120 pubmed publisher
    Accumulating evidence suggests that sphingosine kinase 1 (SphK1)/sphingosine 1-phosphate pathway plays a pivotal role in colon carcinogenesis...
  47. Sun K, Zhang Y, D Alessandro A, Nemkov T, Song A, Wu H, et al. Sphingosine-1-phosphate promotes erythrocyte glycolysis and oxygen release for adaptation to high-altitude hypoxia. Nat Commun. 2016;7:12086 pubmed publisher
    ..altitude on day 1 and continue increasing to 16 days with concurrently elevated erythrocyte sphingonisne kinase 1 (Sphk1) activity and haemoglobin (Hb) oxygen (O2) release capacity...
  48. Frati A, Ricci B, Pierucci F, Nistri S, Bani D, Meacci E. Role of sphingosine kinase/S1P axis in ECM remodeling of cardiac cells elicited by relaxin. Mol Endocrinol. 2015;29:53-67 pubmed publisher
    ..Pharmacological inhibition of sphingolipid metabolism and silencing of sphingosine kinase 1, the enzyme responsible for S1P formation, were able to prevent MMP expression/release elicited by the ..
  49. 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. ..
  50. Wu Y, Mizugishi K, Bektas M, Sandhoff R, Proia R. Sphingosine kinase 1/S1P receptor signaling axis controls glial proliferation in mice with Sandhoff disease. Hum Mol Genet. 2008;17:2257-64 pubmed publisher
    ..When sphingosine kinase 1 (Sphk1) was deleted in Sandhoff disease mice, a milder disease course occurred, with decreased ..
  51. Nava V, Lacana E, Poulton S, Liu H, Sugiura M, Kono K, et al. Functional characterization of human sphingosine kinase-1. FEBS Lett. 2000;473:81-4 pubmed
    ..Thus, hSPHK1 belongs to a highly conserved unique lipid kinase family that regulates diverse biological functions. ..
  52. Zhao Y, Ohkawara H, Rehman J, Wary K, Vogel S, Minshall R, et al. Bone marrow progenitor cells induce endothelial adherens junction integrity by sphingosine-1-phosphate-mediated Rac1 and Cdc42 signaling. Circ Res. 2009;105:696-704, 8 p following 704 pubmed publisher
    ..However, transplantation of BMPCs isolated from sphingosine kinase-1-null mice (SPHK1(-/-)), having impaired S1P production, failed to activate Rac1 and Cdc42 or protect the endothelial barrier...
  53. 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. ..
  54. Nagahashi M, Ramachandran S, Kim E, Allegood J, Rashid O, Yamada A, et al. Sphingosine-1-phosphate produced by sphingosine kinase 1 promotes breast cancer progression by stimulating angiogenesis and lymphangiogenesis. Cancer Res. 2012;72:726-35 pubmed publisher
    ..Here we report pharmacologic evidence of a critical role for sphingosine kinase 1 (SphK1) in producing S1P and mediating tumor-induced hemangiogenesis and lymphangiogenesis in a murine ..
  55. Pchejetski D, Nunes J, Coughlan K, Lall H, Pitson S, Waxman J, et al. The involvement of sphingosine kinase 1 in LPS-induced Toll-like receptor 4-mediated accumulation of HIF-1? protein, activation of ASK1 and production of the pro-inflammatory cytokine IL-6. Immunol Cell Biol. 2011;89:268-74 pubmed publisher
    ..ligand-induced activation of the TLR4 but not TLR7/8 induces activation and transcriptional upregulation of sphingosine kinase 1 (SphK1) in extracellular signal-regulating kinase and phospholipase C-1?/PI3 kinase-dependent manner...
  56. Kono M, Tucker A, Tran J, Bergner J, Turner E, Proia R. Sphingosine-1-phosphate receptor 1 reporter mice reveal receptor activation sites in vivo. J Clin Invest. 2014;124:2076-86 pubmed publisher
    ..Furthermore, this strategy could be potentially applied to any GPCR to identify sites of receptor activation during normal physiology and disease. ..
  57. Camaré C, Trayssac M, Garmy Susini B, Mucher E, Sabbadini R, Salvayre R, et al. Oxidized LDL-induced angiogenesis involves sphingosine 1-phosphate: prevention by anti-S1P antibody. Br J Pharmacol. 2015;172:106-18 pubmed publisher
    ..The angiogenic response to oxLDL was blocked by the sphingosine kinase (SPHK) inhibitor, dimethylsphingosine, by SPHK1-siRNA and by an anti-S1P monoclonal antibody...
  58. Hoefer J, Azam M, Kroetsch J, Leong Poi H, Momen M, Voigtlaender Bolz J, et al. Sphingosine-1-phosphate-dependent activation of p38 MAPK maintains elevated peripheral resistance in heart failure through increased myogenic vasoconstriction. Circ Res. 2010;107:923-33 pubmed publisher
    ..Mice with genetic absence of sphingosine-kinases or S1P(2)R (Sphk1(-/-); Sphk1(-/-)/Sphk2(+/-); S1P(2)R(-/-)) did not manifest enhanced myogenic responses after MI...
  59. Lowe K, Finney B, Deppermann C, Hägerling R, Gazit S, Frampton J, et al. Podoplanin and CLEC-2 drive cerebrovascular patterning and integrity during development. Blood. 2015;125:3769-77 pubmed publisher
  60. Prakash H, Lüth A, Grinkina N, Holzer D, Wadgaonkar R, Gonzalez A, et al. Sphingosine kinase-1 (SphK-1) regulates Mycobacterium smegmatis infection in macrophages. PLoS ONE. 2010;5:e10657 pubmed publisher
    ..Enhanced NO generation and expression of iNOs in SphK-1++ infected macrophages demonstrated their M-1(bright) phenotype of these macrophages. These findings thus suggested a novel antimycobacterial role of SphK-1 in macrophages. ..
  61. Potì F, Ceglarek U, Burkhardt R, Simoni M, Nofer J. SKI-II--a sphingosine kinase 1 inhibitor--exacerbates atherosclerosis in low-density lipoprotein receptor-deficient (LDL-R-/-) mice on high cholesterol diet. Atherosclerosis. 2015;240:212-5 pubmed publisher
    ..25% w/w) or high (1.25% w/w) cholesterol were treated for 16 weeks with SKI-II, a sphingosine kinase 1 inhibitor that significantly reduced plasma S1P levels...
  62. 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
    ..carcinoma cell lines varying in expression of the S1P-degrading enzyme, S1P lyase (SPL) and/or sphingosine kinase (SPHK1). All these cell lines accumulated S1P compared to the wild-type F9 cells, but the amounts varied...
  63. Kalari S, Moolky N, Pendyala S, Berdyshev E, Rolle C, Kanteti R, et al. Sphingosine kinase 1 is required for mesothelioma cell proliferation: role of histone acetylation. PLoS ONE. 2012;7:e45330 pubmed publisher
    ..In this study, we report that the expression of Sphingosine Kinase 1 (SphK1) protein was preferentially elevated in MPM tumor tissues (49 epithelioid and 13 sarcomatoid) ..
  64. Yang J, Noyan Ashraf M, Meissner A, Voigtlaender Bolz J, Kroetsch J, Foltz W, et al. Proximal cerebral arteries develop myogenic responsiveness in heart failure via tumor necrosis factor-?-dependent activation of sphingosine-1-phosphate signaling. Circulation. 2012;126:196-206 pubmed publisher
    ..TNF? mediates its effect via a sphingosine-1-phosphate (S1P)-dependent mechanism, requiring sphingosine kinase 1 and the S1P(2) receptor...
  65. Pfaff M, Powaga N, Akinci S, Schütz W, Banno Y, Wiegand S, et al. Activation of the SPHK/S1P signalling pathway is coupled to muscarinic receptor-dependent regulation of peripheral airways. Respir Res. 2005;6:48 pubmed
    ..In peripheral airways of FVB, wild-type, and MR-deficient mice, SPHK1 was mainly localized to smooth muscle...
  66. Chen J, Wang W, Qi Y, Kaczorowski D, McCaughan G, Gamble J, et al. Deletion of sphingosine kinase 1 ameliorates hepatic steatosis in diet-induced obese mice: Role of PPARγ. Biochim Biophys Acta. 2016;1861:138-147 pubmed publisher
    ..In the present study, we provide both in vitro and in vivo evidence showing a pathogenic role of sphingosine kinase 1 (SphK1) in hepatocellular steatosis...
  67. Lv X, Dai G, Lv G, Chen Y, Wu Y, Shen H, et al. Synergistic interaction of effective parts in Rehmanniae Radix and Cornus officinalis ameliorates renal injury in C57BL/KsJ-db/db diabetic mice: Involvement of suppression of AGEs/RAGE/SphK1 signaling pathway. J Ethnopharmacol. 2016;185:110-9 pubmed publisher
    ..the present study were to investigate the renoprotective effects of CBP on DN through the inhibition of AGEs/RAGE/SphK1 signaling pathway activation, and identify the advantage of CBP compared with IGCO, TACO, IGRR...
  68. Shu X, Wu W, Mosteller R, Broek D. Sphingosine kinase mediates vascular endothelial growth factor-induced activation of ras and mitogen-activated protein kinases. Mol Cell Biol. 2002;22:7758-68 pubmed
    ..Small interfering RNA (siRNA) that targets SPK1, but not SPK2, blocks VEGF-induced accumulation of Ras-GTP and phospho-ERK in T24 cells...