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Gene Review

SPHK1  -  sphingosine kinase 1

Homo sapiens

Synonyms: SK 1, SPHK, SPK, SPK 1, Sphingosine kinase 1
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Disease relevance of SPHK1


High impact information on SPHK1


Chemical compound and disease context of SPHK1


Biological context of SPHK1


Anatomical context of SPHK1


Associations of SPHK1 with chemical compounds


Physical interactions of SPHK1


Enzymatic interactions of SPHK1

  • These studies demonstrate that SK1 is cleaved by cathepsin B in a sequential manner after basic amino acids, and that the initial cleavages at the two identified sites occur independently of each other [27].
  • In vitro phosphatase assays showed that PP2Ac dephosphorylated both recombinant SK1 and a phosphopeptide based on the phospho-Ser(225) region of SK1 [28].

Regulatory relationships of SPHK1

  • Interestingly, only depletion of PKC-alpha leads to a complete loss of TPA- and histamine-triggered SK-1 induction and cell migration [29].
  • These data show that SPHK1 participates in the dbcAMP-induced differentiation of HL60 cells by activating the MEK/ERK pathway [30].
  • In this study, we show that in the human breast cancer cell line MCF7, epidermal growth factor (EGF) stimulates SK-1 activity in a biphasic manner with a first peak after 15 min and a second delayed activation occurring after 1 h up to 18 h and thereafter declining again [31].
  • In this study, we show that prolonged treatment of MCF-7 cells with tumor necrosis factor (TNF) induces a dose- and time-dependent decrease in SK1 protein [32].
  • In BMM single cultures, the osteoclastogenic factor receptor activator of NF-kappaB ligand (RANKL) upregulated SPHK1 and increased S1P production and secretion [33].

Other interactions of SPHK1


Analytical, diagnostic and therapeutic context of SPHK1


  1. Sphingosine kinase type 1 promotes estrogen-dependent tumorigenesis of breast cancer MCF-7 cells. Nava, V.E., Hobson, J.P., Murthy, S., Milstien, S., Spiegel, S. Exp. Cell Res. (2002) [Pubmed]
  2. Sphingosine kinase protects lipopolysaccharide-activated macrophages from apoptosis. Wu, W., Mosteller, R.D., Broek, D. Mol. Cell. Biol. (2004) [Pubmed]
  3. Sphingosine kinase mediates activation of extracellular signal-related kinase and Akt by respiratory syncytial virus. Monick, M.M., Cameron, K., Powers, L.S., Butler, N.S., McCoy, D., Mallampalli, R.K., Hunninghake, G.W. Am. J. Respir. Cell Mol. Biol. (2004) [Pubmed]
  4. The effect of hypoxia on lipid phosphate receptor and sphingosine kinase expression and mitogen-activated protein kinase signaling in human pulmonary smooth muscle cells. Ahmad, M., Long, J.S., Pyne, N.J., Pyne, S. Prostaglandins Other Lipid Mediat. (2006) [Pubmed]
  5. Enhancement of SPHK1 in vitro by carbon ion irradiation in oral squamous cell carcinoma. Higo, M., Uzawa, K., Kawata, T., Kato, Y., Kouzu, Y., Yamamoto, N., Shibahara, T., Mizoe, J.E., Ito, H., Tsujii, H., Tanzawa, H. Int. J. Radiat. Oncol. Biol. Phys. (2006) [Pubmed]
  6. Sphingosine kinase 1 is up-regulated during hypoxia in U87MG glioma cells. Role of hypoxia-inducible factors 1 and 2. Anelli, V., Gault, C.R., Cheng, A.B., Obeid, L.M. J. Biol. Chem. (2008) [Pubmed]
  7. Clinical significance of sphingosine kinase-1 expression in human astrocytomas progression and overall patient survival. Li, J., Guan, H.Y., Gong, L.Y., Song, L.B., Zhang, N., Wu, J., Yuan, J., Zheng, Y.J., Huang, Z.S., Li, M. Clin. Cancer Res. (2008) [Pubmed]
  8. Suppression of ceramide-mediated programmed cell death by sphingosine-1-phosphate. Cuvillier, O., Pirianov, G., Kleuser, B., Vanek, P.G., Coso, O.A., Gutkind, S., Spiegel, S. Nature (1996) [Pubmed]
  9. Calcium mobilization via sphingosine kinase in signalling by the Fc epsilon RI antigen receptor. Choi, O.H., Kim, J.H., Kinet, J.P. Nature (1996) [Pubmed]
  10. Sphingosine-1-phosphate as second messenger in cell proliferation induced by PDGF and FCS mitogens. Olivera, A., Spiegel, S. Nature (1993) [Pubmed]
  11. The sphingosine kinase-sphingosine-1-phosphate axis is a determinant of mast cell function and anaphylaxis. Olivera, A., Mizugishi, K., Tikhonova, A., Ciaccia, L., Odom, S., Proia, R.L., Rivera, J. Immunity (2007) [Pubmed]
  12. Sphingosine kinase 1 (SK1) is recruited to nascent phagosomes in human macrophages: inhibition of SK1 translocation by Mycobacterium tuberculosis. Thompson, C.R., Iyer, S.S., Melrose, N., VanOosten, R., Johnson, K., Pitson, S.M., Obeid, L.M., Kusner, D.J. J. Immunol. (2005) [Pubmed]
  13. High expression of sphingosine kinase 1 and S1P receptors in chemotherapy-resistant prostate cancer PC3 cells and their camptothecin-induced up-regulation. Akao, Y., Banno, Y., Nakagawa, Y., Hasegawa, N., Kim, T.J., Murate, T., Igarashi, Y., Nozawa, Y. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  14. Activation of the sphingosine kinase-signaling pathway by high glucose mediates the proinflammatory phenotype of endothelial cells. Wang, L., Xing, X.P., Holmes, A., Wadham, C., Gamble, J.R., Vadas, M.A., Xia, P. Circ. Res. (2005) [Pubmed]
  15. Sphingosine kinase-1 as a chemotherapy sensor in prostate adenocarcinoma cell and mouse models. Pchejetski, D., Golzio, M., Bonhoure, E., Calvet, C., Doumerc, N., Garcia, V., Mazerolles, C., Rischmann, P., Teissié, J., Malavaud, B., Cuvillier, O. Cancer Res. (2005) [Pubmed]
  16. Phosphorylation of the immunomodulatory drug FTY720 by sphingosine kinases. Billich, A., Bornancin, F., Dévay, P., Mechtcheriakova, D., Urtz, N., Baumruker, T. J. Biol. Chem. (2003) [Pubmed]
  17. Cloning and characterization of a protein kinase A anchoring protein (AKAP)-related protein that interacts with and regulates sphingosine kinase 1 activity. Lacaná, E., Maceyka, M., Milstien, S., Spiegel, S. J. Biol. Chem. (2002) [Pubmed]
  18. Antisense knockdown of sphingosine kinase 1 in human macrophages inhibits C5a receptor-dependent signal transduction, Ca2+ signals, enzyme release, cytokine production, and chemotaxis. Melendez, A.J., Ibrahim, F.B. J. Immunol. (2004) [Pubmed]
  19. Molecular cloning and functional characterization of a novel mammalian sphingosine kinase type 2 isoform. Liu, H., Sugiura, M., Nava, V.E., Edsall, L.C., Kono, K., Poulton, S., Milstien, S., Kohama, T., Spiegel, S. J. Biol. Chem. (2000) [Pubmed]
  20. Basal and induced sphingosine kinase 1 activity in A549 carcinoma cells: function in cell survival and IL-1beta and TNF-alpha induced production of inflammatory mediators. Billich, A., Bornancin, F., Mechtcheriakova, D., Natt, F., Huesken, D., Baumruker, T. Cell. Signal. (2005) [Pubmed]
  21. Anaphylatoxin signaling in human neutrophils. A key role for sphingosine kinase. Ibrahim, F.B., Pang, S.J., Melendez, A.J. J. Biol. Chem. (2004) [Pubmed]
  22. Identification and characterization of RPK118, a novel sphingosine kinase-1-binding protein. Hayashi, S., Okada, T., Igarashi, N., Fujita, T., Jahangeer, S., Nakamura, S. J. Biol. Chem. (2002) [Pubmed]
  23. Sphingosine kinase mediates vascular endothelial growth factor-induced activation of ras and mitogen-activated protein kinases. Shu, X., Wu, W., Mosteller, R.D., Broek, D. Mol. Cell. Biol. (2002) [Pubmed]
  24. Sphingosine kinase-1 enhances endothelial cell survival through a PECAM-1-dependent activation of PI-3K/Akt and regulation of Bcl-2 family members. Limaye, V., Li, X., Hahn, C., Xia, P., Berndt, M.C., Vadas, M.A., Gamble, J.R. Blood (2005) [Pubmed]
  25. Sphingosine kinase isoforms regulate oxaliplatin sensitivity of human colon cancer cells through ceramide accumulation and Akt activation. Nemoto, S., Nakamura, M., Osawa, Y., Kono, S., Itoh, Y., Okano, Y., Murate, T., Hara, A., Ueda, H., Nozawa, Y., Banno, Y. J. Biol. Chem. (2009) [Pubmed]
  26. Formyl peptide receptor signaling in HL-60 cells through sphingosine kinase. Alemany, R., Meyer zu Heringdorf, D., van Koppen, C.J., Jakobs, K.H. J. Biol. Chem. (1999) [Pubmed]
  27. Sphingosine kinase-1 is cleaved by cathepsin B in vitro: Identification of the initial cleavage sites for the protease. Taha, T.A., El-Alwani, M., Hannun, Y.A., Obeid, L.M. FEBS Lett. (2006) [Pubmed]
  28. Deactivation of sphingosine kinase 1 by protein phosphatase 2A. Barr, R.K., Lynn, H.E., Moretti, P.A., Khew-Goodall, Y., Pitson, S.M. J. Biol. Chem. (2008) [Pubmed]
  29. Histamine increases sphingosine kinase-1 expression and activity in the human arterial endothelial cell line EA.hy 926 by a PKC-alpha-dependent mechanism. Huwiler, A., Döll, F., Ren, S., Klawitter, S., Greening, A., Römer, I., Bubnova, S., Reinsberg, L., Pfeilschifter, J. Biochim. Biophys. Acta (2006) [Pubmed]
  30. Sphingosine kinase 1 is involved in dibutyryl cyclic AMP-induced granulocytic differentiation through the upregulation of extracellular signal-regulated kinase, but not p38 MAP kinase, in HL60 cells. Koda, M., Murate, T., Wang, S., Ohguchi, K., Sobue, S., Ikeda, M., Tamiya-Koizumi, K., Igarashi, Y., Nozawa, Y., Banno, Y. Biochim. Biophys. Acta (2005) [Pubmed]
  31. The epidermal growth factor stimulates sphingosine kinase-1 expression and activity in the human mammary carcinoma cell line MCF7. Döll, F., Pfeilschifter, J., Huwiler, A. Biochim. Biophys. Acta (2005) [Pubmed]
  32. Tumor necrosis factor induces the loss of sphingosine kinase-1 by a cathepsin B-dependent mechanism. Taha, T.A., Kitatani, K., Bielawski, J., Cho, W., Hannun, Y.A., Obeid, L.M. J. Biol. Chem. (2005) [Pubmed]
  33. Sphingosine 1-phosphate as a regulator of osteoclast differentiation and osteoclast-osteoblast coupling. Ryu, J., Kim, H.J., Chang, E.J., Huang, H., Banno, Y., Kim, H.H. EMBO J. (2006) [Pubmed]
  34. Involvement of N-terminal-extended form of sphingosine kinase 2 in serum-dependent regulation of cell proliferation and apoptosis. Okada, T., Ding, G., Sonoda, H., Kajimoto, T., Haga, Y., Khosrowbeygi, A., Gao, S., Miwa, N., Jahangeer, S., Nakamura, S. J. Biol. Chem. (2005) [Pubmed]
  35. The Calmodulin-binding Site of Sphingosine Kinase and Its Role in Agonist-dependent Translocation of Sphingosine Kinase 1 to the Plasma Membrane. Sutherland, C.M., Moretti, P.A., Hewitt, N.M., Bagley, C.J., Vadas, M.A., Pitson, S.M. J. Biol. Chem. (2006) [Pubmed]
  36. Sphingosine kinase 1-mediated inhibition of Fas death signaling in rheumatoid arthritis B lymphoblastoid cells. Pi, X., Tan, S.Y., Hayes, M., Xiao, L., Shayman, J.A., Ling, S., Holoshitz, J. Arthritis Rheum. (2006) [Pubmed]
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