Gene Symbol: Sphk1
Description: sphingosine kinase 1
Alias: sphingosine kinase 1, SK 1, SPK 1
Species: rat
Products:     Sphk1

Top Publications

  1. Pilorget A, Demeule M, Barakat S, Marvaldi J, Luis J, Beliveau R. Modulation of P-glycoprotein function by sphingosine kinase-1 in brain endothelial cells. J Neurochem. 2007;100:1203-10 pubmed
    ..Here, we have investigated the regulation of P-gp transport activity by sphingosine kinase 1 (SphK-1) in brain endothelial cells...
  2. 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. ..
  3. Jolly P, Bektas M, Watterson K, Sankala H, Payne S, Milstien S, et al. Expression of SphK1 impairs degranulation and motility of RBL-2H3 mast cells by desensitizing S1P receptors. Blood. 2005;105:4736-42 pubmed
    ..b>Sphingosine kinase 1 (SphK1) and formation of S1P, which leads to transactivation of S1P receptors and their downstream ..
  4. Anelli V, Bassi R, Tettamanti G, Viani P, Riboni L. Extracellular release of newly synthesized sphingosine-1-phosphate by cerebellar granule cells and astrocytes. J Neurochem. 2005;92:1204-15 pubmed
    ..Phorbol ester treatment resulted in an increase in sphingosine kinase 1 activity in the membranes, accompanied by a significant increase in extracellular S1P...
  5. Wu W, Mosteller R, Broek D. Sphingosine kinase protects lipopolysaccharide-activated macrophages from apoptosis. Mol Cell Biol. 2004;24:7359-69 pubmed
    ..These data demonstrate the critical role of SPK1 in LPS signaling in macrophages and suggest that SPK1 is a potential therapeutic target to block hyperimmune responses induced by gram-negative bacteria. ..
  6. Pitson S, D Andrea R, Vandeleur L, Moretti P, Xia P, Gamble J, et al. Human sphingosine kinase: purification, molecular cloning and characterization of the native and recombinant enzymes. Biochem J. 2000;350 Pt 2:429-41 pubmed
    ..In all cases, both the native and recombinant SKs displayed remarkably similar properties, indicating that post-translational modifications are not required for basal activity of human SK. ..
  7. Kajimoto T, Okada T, Yu H, Goparaju S, Jahangeer S, Nakamura S. Involvement of sphingosine-1-phosphate in glutamate secretion in hippocampal neurons. Mol Cell Biol. 2007;27:3429-40 pubmed
    ..b>Sphingosine kinase 1 (SK1), a key enzyme for S1P production, was enriched in functional puncta of hippocampal neurons...
  8. Nava V, Hobson J, Murthy S, Milstien S, Spiegel S. Sphingosine kinase type 1 promotes estrogen-dependent tumorigenesis of breast cancer MCF-7 cells. Exp Cell Res. 2002;281:115-27 pubmed
    ..Enforced expression of sphingosine kinase type 1 (SPHK1) increased S1P levels and blocked MCF-7 cell death induced by anti-cancer drugs, sphingosine, and TNF-alpha...
  9. Facchinetti M, Leocata Nieto F, Marquez M, Sterin Speziale N. Stratification of sphingosine kinase-1 expression and activity in rat kidney. Cells Tissues Organs. 2008;188:384-92 pubmed publisher
    ..We also evaluated the effects of bradykinin and angiotensin II on SK1 activity. ..

More Information


  1. Saini H, Coelho R, Goparaju S, Jolly P, Maceyka M, Spiegel S, et al. Novel role of sphingosine kinase 1 as a mediator of neurotrophin-3 action in oligodendrocyte progenitors. J Neurochem. 2005;95:1298-310 pubmed
    ..Moreover, CREB phosphorylation in response to NT-3 involves sphingosine kinase 1 (SphK1), the enzyme that synthesizes S1P...
  2. 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...
  3. Kawamori T, Osta W, Johnson K, Pettus B, Bielawski J, Tanaka T, et al. Sphingosine kinase 1 is up-regulated in colon carcinogenesis. FASEB J. 2006;20:386-8 pubmed
    b>Sphingosine kinase 1 (SK1) phosphorylates sphingosine to form sphingosine 1-phosphate (S1P), which has the ability to promote cell proliferation and survival and stimulate angiogenesis...
  4. Spijkers L, Alewijnse A, Peters S. FTY720 (fingolimod) increases vascular tone and blood pressure in spontaneously hypertensive rats via inhibition of sphingosine kinase. Br J Pharmacol. 2012;166:1411-8 pubmed publisher
    ..These data demonstrate that FTY720 increases vascular tone and BP only in hypertensive rats, most likely as a result of its inhibitory effect on sphingosine kinase. ..
  5. Bolz S, Vogel L, Sollinger D, Derwand R, Boer C, Pitson S, et al. Sphingosine kinase modulates microvascular tone and myogenic responses through activation of RhoA/Rho kinase. Circulation. 2003;108:342-7 pubmed
    RhoA and Rho kinase are important modulators of microvascular tone. We tested whether sphingosine kinase (Sphk1) that generates the endogenous sphingolipid mediator sphingosine-1-phosphate (S1P) is part of a signaling cascade to activate ..
  6. 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) ..
  7. Lufrano M, Jacob A, Zhou M, Wang P. Sphingosine kinase?1 mediates endotoxemia?induced hyperinflammation in aged animals. Mol Med Rep. 2013;8:645-9 pubmed publisher
    ..Results of the present study indicated that increased Sphk?1 expression in the liver in response to endotoxemia mediates the hyperinflammatory state observed in aged animals. ..
  8. Moruno Manchon J, Uzor N, Finkbeiner S, Tsvetkov A. SPHK1/sphingosine kinase 1-mediated autophagy differs between neurons and SH-SY5Y neuroblastoma cells. Autophagy. 2016;12:1418-24 pubmed publisher
    ..In a recent study, we sought to determine if SPHK1 (sphingosine kinase 1), implicated previously in macroautophagy/autophagy in cancer cells, regulates autophagy in neurons...
  9. Lv M, Zhang D, Dai D, Zhang W, Zhang L. Sphingosine kinase 1/sphingosine-1-phosphate regulates the expression of interleukin-17A in activated microglia in cerebral ischemia/reperfusion. Inflamm Res. 2016;65:551-62 pubmed publisher
    ..b>Sphingosine kinase 1 (Sphk1), a key enzyme responsible for phosphorylating sphingosine into sphingosine-1-phosphate (S1P), plays ..
  10. Serrano Sanchez M, Tanfin Z, Leiber D. Signaling pathways involved in sphingosine kinase activation and sphingosine-1-phosphate release in rat myometrium in late pregnancy: role in the induction of cyclooxygenase 2. Endocrinology. 2008;149:4669-79 pubmed publisher
    ..b>SphK1 and SphK2 were coexpressed in myometrium during gestation...
  11. 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. ..
  12. Sobue S, Hagiwara K, Banno Y, Tamiya Koizumi K, Suzuki M, Takagi A, et al. Transcription factor specificity protein 1 (Sp1) is the main regulator of nerve growth factor-induced sphingosine kinase 1 gene expression of the rat pheochromocytoma cell line, PC12. J Neurochem. 2005;95:940-9 pubmed
    ..We previously reported that human brain is rich in SPHK1 (Murate et al. 2001)...
  13. Mastrandrea L, Sessanna S, Laychock S. Sphingosine kinase activity and sphingosine-1 phosphate production in rat pancreatic islets and INS-1 cells: response to cytokines. Diabetes. 2005;54:1429-36 pubmed
    ..SPHK2 was the predominant active isoform in INS-1 cells; little or no SPHK1 activity was detected...
  14. Delon C, Manifava M, Wood E, Thompson D, Krugmann S, Pyne S, et al. Sphingosine kinase 1 is an intracellular effector of phosphatidic acid. J Biol Chem. 2004;279:44763-74 pubmed
    b>Sphingosine kinase 1 (SK1) phosphorylates sphingosine to generate sphingosine 1-phosphate (S1P)...
  15. Coste O, Brenneis C, Linke B, Pierre S, Maeurer C, Becker W, et al. Sphingosine 1-phosphate modulates spinal nociceptive processing. J Biol Chem. 2008;283:32442-51 pubmed publisher
    ..inhibition of sphingosine kinases (SPHK) decreased basal pain thresholds and SphK2 knock-out mice, but not SphK1 knock-out mice, had a significant decrease in withdrawal latency...
  16. Hasan N, Longacre M, Stoker S, Kendrick M, Druckenbrod N, Laychock S, et al. Sphingosine kinase 1 knockdown reduces insulin synthesis and secretion in a rat insulinoma cell line. Arch Biochem Biophys. 2012;518:23-30 pubmed publisher
    To evaluate the role of sphingosine kinase 1 (SphK1) in insulin secretion, we used stable transfection to knock down the expression of the Sphk1 gene in the rat insulinoma INS-1 832/13 cell line...
  17. Park C, Lee H, Lee H, Park C, Choi O. Cloning and characterization of rat sphingosine kinase 1 with an N-terminal extension. Biochem Biophys Res Commun. 2007;364:702-7 pubmed
    ..Taken together, the fact that long-rSK1 with similar enzymatic characteristics to rSK1 displays differential tissue distribution may suggest an additional role of long-rSK1. ..
  18. Imamura T, Ohgane J, Ito S, Ogawa T, Hattori N, Tanaka S, et al. CpG island of rat sphingosine kinase-1 gene: tissue-dependent DNA methylation status and multiple alternative first exons. Genomics. 2001;76:117-25 pubmed
    It is generally recognized that CpG islands are not methylated in normal tissues. SPHK1 is a key enzyme catalyzing the production of sphingosine 1-phosphate, a novel signaling molecule for the proliferation and differentiation of various ..
  19. Toman R, Payne S, Watterson K, Maceyka M, Lee N, Milstien S, et al. Differential transactivation of sphingosine-1-phosphate receptors modulates NGF-induced neurite extension. J Cell Biol. 2004;166:381-92 pubmed
    ..Stimulation of sphingosine kinase 1 (SphK1), the enzyme that phosphorylates sphingosine to form sphingosine-1-phosphate (S1P), is part of the ..
  20. Mastrandrea L, Sessanna S, Del Toro A, Laychock S. ATP-independent glucose stimulation of sphingosine kinase in rat pancreatic islets. J Lipid Res. 2010;51:2171-80 pubmed publisher
    ..Glucose-supported beta-cell growth appears to be in part mediated by SPHK activity. ..
  21. Su D, Cheng Y, Li S, Dai D, Zhang W, Lv M. Sphk1 mediates neuroinflammation and neuronal injury via TRAF2/NF-κB pathways in activated microglia in cerebral ischemia reperfusion. J Neuroimmunol. 2017;305:35-41 pubmed publisher
    b>Sphingosine kinase 1 (Sphk1), a key enzyme responsible for phosphorylating sphingosine into sphingosine1-phosphate (S1P), plays an important role in mediating post-stroke neuroinflammation...
  22. Sun J, Yan G, Ren A, You B, Liao J. FHL2/SLIM3 decreases cardiomyocyte survival by inhibitory interaction with sphingosine kinase-1. Circ Res. 2006;99:468-76 pubmed
    ..These findings indicate that FHL2 is a novel inhibitor of SK1 activity in cardiomyocytes and suggest that targeting FHL2 for inhibition may prevent myocardial apoptosis through activation of SK1. ..
  23. Lin H, Baby N, Lu J, Kaur C, Zhang C, Xu J, et al. Expression of sphingosine kinase 1 in amoeboid microglial cells in the corpus callosum of postnatal rats. J Neuroinflammation. 2011;8:13 pubmed publisher
    b>Sphingosine kinase 1 (SphK1), a key enzyme responsible for phosphorylating sphingosine into sphingosine-1-phosphate (S1P) has been shown to be expressed in monocytes and monocyte-derived peripheral macrophages...
  24. Pitson S, Xia P, Leclercq T, Moretti P, Zebol J, Lynn H, et al. Phosphorylation-dependent translocation of sphingosine kinase to the plasma membrane drives its oncogenic signalling. J Exp Med. 2005;201:49-54 pubmed
    ..Thus, phosphorylation of hSK1 is essential for oncogenic signaling, and is brought about through phosphorylation-induced translocation of hSK1 to the plasma membrane, rather than from enhanced catalytic activity of this enzyme. ..
  25. Fischer I, Alliod C, Martinier N, Newcombe J, Brana C, Pouly S. Sphingosine kinase 1 and sphingosine 1-phosphate receptor 3 are functionally upregulated on astrocytes under pro-inflammatory conditions. PLoS ONE. 2011;6:e23905 pubmed publisher
    ..The sphingosine kinase 1 (SphK1)/sphingosine1-phosphate (S1P) receptor signaling pathway is involved in modulation of the ..
  26. Raymond M, Bole Feysot C, Banno Y, Tanfin Z, Robin P. Endothelin-1 inhibits apoptosis through a sphingosine kinase 1-dependent mechanism in uterine leiomyoma ELT3 cells. Endocrinology. 2006;147:5873-82 pubmed
    ..However, inhibitors of sphingosine kinase-1 (SphK1), dimethylsphingosine and threo-dihydrosphingosine, reduced the effect of ET-1 by about 50%...
  27. Lan T, Liu W, Xie X, Xu S, Huang K, Peng J, et al. Sphingosine kinase-1 pathway mediates high glucose-induced fibronectin expression in glomerular mesangial cells. Mol Endocrinol. 2011;25:2094-105 pubmed publisher
    ..The SphK1 pathway and FN expression were examined in streptozotocin-induced diabetic rat kidney and glomerular mesangial ..
  28. Jeng Y, Suarez V, Izban M, Wang H, Soloff M. Progesterone-induced sphingosine kinase-1 expression in the rat uterus during pregnancy and signaling consequences. Am J Physiol Endocrinol Metab. 2007;292:E1110-21 pubmed
    ..Of these, only sphingosine kinase-1 (SphK1) was markedly changed ( approximately 30-fold increase), being localized in the glandular epithelium, vasculature, ..
  29. Melendez A, Carlos Dias E, Gosink M, Allen J, Takacs L. Human sphingosine kinase: molecular cloning, functional characterization and tissue distribution. Gene. 2000;251:19-26 pubmed
    ..It is also expressed in brain and heart. In addition, database searches with the stSG2854 sequence indicate that huSPHK1 is also expressed in endothelial cells, retinal pigment epithelium, and senescent fibroblasts. ..
  30. Xu M, Liu D, Ding L, Ma K, Wu M, Lv L, et al. FTY720 inhibits tubulointerstitial inflammation in albumin overload-induced nephropathy of rats via the Sphk1 pathway. Acta Pharmacol Sin. 2014;35:1537-45 pubmed publisher
    ..and IL-6, as well as sphingosine 1-phosphate (S1P) receptors S1pr1 and S1pr3, and S1P-synthesizing enzyme sphingosine kinase 1 (Sphk1) in the kidney...
  31. Lei S, Wang Q, Lv C, Wu C, Yuan Q, Han J. [Inhibition of S1PR2 activity down-regulates expressions of sphingosine kinase 1 and MCP-1 in rat glomerular mesangial cells under high glucose]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2015;31:36-9 pubmed
    ..and the specific antagonist JTE-013 of sphingosine-1-phosphate receptor 2 (S1PR2) on the expressions of sphingosine kinase 1 (Sphk1), S1PR2 and monocyte chemoattractant protein-1 (MCP-1) in rat glomerular mesangial cells...
  32. Lan T, Liu W, Xie X, Huang K, Peng J, Huang J, et al. Berberine suppresses high glucose-induced TGF-?1 and fibronectin synthesis in mesangial cells through inhibition of sphingosine kinase 1/AP-1 pathway. Eur J Pharmacol. 2012;697:165-72 pubmed publisher
    b>Sphingosine kinase 1 (SphK1) pathway is critical in the pathogenesis of diabetic nephropathy. Recently, we found that berberine suppressed the activation of SphK1 pathway in diabetic kidney, protecting against diabetic nephropathy...
  33. Pitson S, Moretti P, Zebol J, Zareie R, Derian C, Darrow A, et al. The nucleotide-binding site of human sphingosine kinase 1. J Biol Chem. 2002;277:49545-53 pubmed
    ..Here we have elucidated the nucleotide-binding site of human sphingosine kinase 1 (hSK1) through a combination of site-directed mutagenesis and affinity labeling with the ATP analogue, FSBA...
  34. Jarman K, Moretti P, Zebol J, Pitson S. Translocation of sphingosine kinase 1 to the plasma membrane is mediated by calcium- and integrin-binding protein 1. J Biol Chem. 2010;285:483-92 pubmed publisher
    SK1 (sphingosine kinase 1) plays an important role in many aspects of cellular regulation...
  35. Pitman M, Barr R, Gliddon B, Magarey A, Moretti P, Pitson S. A critical role for the protein phosphatase 2A B'? regulatory subunit in dephosphorylation of sphingosine kinase 1. Int J Biochem Cell Biol. 2011;43:342-7 pubmed publisher
    b>Sphingosine kinase 1 (SK1) is an important regulator of cellular signalling that has gained recent attention as a potential target for anti-cancer therapies...
  36. Sorice M, Molinari S, Di Marzio L, Mattei V, Tasciotti V, Ciarlo L, et al. Neurotrophic signalling pathway triggered by prosaposin in PC12 cells occurs through lipid rafts. FEBS J. 2008;275:4903-12 pubmed publisher
    ..These findings point to the role of lipid rafts in the prosaposin-triggered signalling pathway, thus supporting a role for this factor as a new component of the multimolecular signalling complex involved in the neurotrophic response. ..
  37. Cieślik M, Czapski G, Strosznajder J. The Molecular Mechanism of Amyloid β42 Peptide Toxicity: The Role of Sphingosine Kinase-1 and Mitochondrial Sirtuins. PLoS ONE. 2015;10:e0137193 pubmed publisher
    ..b>SphK1 is a key enzyme involved in maintaining sphingolipid rheostat in the brain...
  38. Gratschev D, Löf C, Heikkila J, Björkbom A, Sukumaran P, Hinkkanen A, et al. Sphingosine kinase as a regulator of calcium entry through autocrine sphingosine 1-phosphate signaling in thyroid FRTL-5 cells. Endocrinology. 2009;150:5125-34 pubmed publisher
    ..Here, we have described the importance of sphingosine, sphingosine kinase 1 (SK1), and sphingosine 1-phosphate (S1P) in regulating calcium entry in thyroid FRTL-5 cells...
  39. Ma M, Chen J, Wang G, Wang H, Lu Y, Li J, et al. Sphingosine kinase 1 participates in insulin signalling and regulates glucose metabolism and homeostasis in KK/Ay diabetic mice. Diabetologia. 2007;50:891-900 pubmed
    The aim of this study was to determine the potential role of sphingosine kinase 1 (SPHK1), a key sphingolipid metabolic enzyme, in glucose metabolism and homeostasis...
  40. Gandy K, Canals D, Adada M, Wada M, Roddy P, Snider A, et al. Sphingosine 1-phosphate induces filopodia formation through S1PR2 activation of ERM proteins. Biochem J. 2013;449:661-72 pubmed publisher
    ..Taken together, the results demonstrate a novel mechanism by which S1P regulates cellular architecture that requires S1PR2 and subsequent phosphorylation of ERM proteins...
  41. Miranda G, Abrahan C, Politi L, Rotstein N. Sphingosine-1-phosphate is a key regulator of proliferation and differentiation in retina photoreceptors. Invest Ophthalmol Vis Sci. 2009;50:4416-28 pubmed publisher
    ..The authors propose S1P as a key regulator in photoreceptor development. GDNF and DHA might upregulate SphK levels to promote S1P synthesis, which would initially promote proliferation and then advance photoreceptor differentiation. ..
  42. Leiber D, Banno Y, Tanfin Z. Exogenous sphingosine 1-phosphate and sphingosine kinase activated by endothelin-1 induced myometrial contraction through differential mechanisms. Am J Physiol Cell Physiol. 2007;292:C240-50 pubmed
    ..ET-1, via ET(A) receptors coupled to pertussis toxin-insensitive G proteins, stimulated SphK1 activity and induced its translocation to the membranes...
  43. Klawitter S, Hofmann L, Pfeilschifter J, Huwiler A. Extracellular nucleotides induce migration of renal mesangial cells by upregulating sphingosine kinase-1 expression and activity. Br J Pharmacol. 2007;150:271-80 pubmed
    ..Thus, pharmacological intervention of SK-1 may have impacts on situations where MC migration is important such as during inflammatory kidney diseases. ..
  44. Imamura T, Miyauchi Senda N, Tanaka S, Shiota K. Identification of genetic and epigenetic similarities of SPHK1/Sphk1 in mammals. J Vet Med Sci. 2004;66:1387-93 pubmed
    ..Gene Sphk1 has shown complex organization, indicated by multiple alternative splicing and tissue-dependent DNA methylation ..
  45. Pchejetski D, Kunduzova O, Dayon A, Calise D, Seguelas M, Leducq N, et al. Oxidative stress-dependent sphingosine kinase-1 inhibition mediates monoamine oxidase A-associated cardiac cell apoptosis. Circ Res. 2007;100:41-9 pubmed
    ..reactive oxygen species generation led to mitochondria-mediated apoptosis, along with sphingosine kinase-1 (SphK1) inhibition...
  46. Kanno T, Nishizaki T. Sphingosine induces apoptosis in hippocampal neurons and astrocytes by activating caspase-3/-9 via a mitochondrial pathway linked to SDK/14-3-3 protein/Bax/cytochrome c. J Cell Physiol. 2011;226:2329-37 pubmed publisher
  47. Huang K, Huang J, Chen C, Hao J, Wang S, Huang J, et al. AP-1 regulates sphingosine kinase 1 expression in a positive feedback manner in glomerular mesangial cells exposed to high glucose. Cell Signal. 2014;26:629-38 pubmed publisher
    Our previous studies have confirmed that the sphingosine kinase 1 (SphK1)-sphingosine 1-phosphate (S1P) signaling pathway in the kidney under diabetic conditions is closely correlated with the pathogenesis of diabetic nephropathy (DN)...
  48. Ryu S, Lee H, Suk H, Park C, Choi O. Cross-linking of FcepsilonRI causes Ca2+ mobilization via a sphingosine kinase pathway in a clathrin-dependent manner. Cell Calcium. 2009;45:99-108 pubmed publisher
    ..The present study identifies the SK/Ca(2+) pathway to be dependent on clathrin. ..