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Gene Review

SPHK2  -  sphingosine kinase 2

Homo sapiens

Synonyms: SK 2, SK-2, SPK 2, SPK-2, Sphingosine kinase 2
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Disease relevance of SPHK2

  • Thus SK2 is a renal epithelial protein kinase whose expression and activity are increased during development and recovery from acute renal failure, where tubular epithelial regeneration may recapitulate developmental processes [1].
  • In cultured renal tubular epithelial cells, SK2 kinase activity was increased after incubation with serum, or after exposure to chemical anoxia plus reexposure to glucose [1].
  • Transduction of Chinese hamster ovary cells with a recombinant adenovirus encoding the hSK2-green fluorescent protein fusion construct resulted in expression of functional apamin-sensitive K(+) channels [2].

High impact information on SPHK2


Biological context of SPHK2


Anatomical context of SPHK2


Associations of SPHK2 with chemical compounds


Other interactions of SPHK2

  • Unlike the proliferative action of SPHK1, another isozyme, SPHK2, has been shown to possess anti-proliferative or pro-apoptotic action [7].
  • Increased SPHK-1 (but not SPHK-2) mRNA levels were observed in synovial tissue from RA patients [17].

Analytical, diagnostic and therapeutic context of SPHK2

  • By immunohistochemistry, SK2 expression was evident mainly in the cytoplasm of tubular epithelial cells in fetal and adult kidneys [1].
  • In adult kidneys subjected to cross-clamping of the renal artery, followed by reperfusion, SK2 mRNA, protein expression, and kinase activity were increased compared with untreated contralateral controls [1].


  1. Renal expression and activity of the germinal center kinase SK2. Cybulsky, A.V., Takano, T., Papillon, J., Khadir, A., Bijian, K., Chien, C.C., Alpers, C.E., Rabb, H. Am. J. Physiol. Renal Physiol. (2004) [Pubmed]
  2. Molecular characterization of volume-sensitive SK(Ca) channels in human liver cell lines. Roman, R., Feranchak, A.P., Troetsch, M., Dunkelberg, J.C., Kilic, G., Schlenker, T., Schaack, J., Fitz, J.G. Am. J. Physiol. Gastrointest. Liver Physiol. (2002) [Pubmed]
  3. 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]
  4. Genome sequence of the ubiquitous hydrocarbon-degrading marine bacterium Alcanivorax borkumensis. Schneiker, S., Martins dos Santos, V.A., Bartels, D., Bekel, T., Brecht, M., Buhrmester, J., Chernikova, T.N., Denaro, R., Ferrer, M., Gertler, C., Goesmann, A., Golyshina, O.V., Kaminski, F., Khachane, A.N., Lang, S., Linke, B., McHardy, A.C., Meyer, F., Nechitaylo, T., Pühler, A., Regenhardt, D., Rupp, O., Sabirova, J.S., Selbitschka, W., Yakimov, M.M., Timmis, K.N., Vorhölter, F.J., Weidner, S., Kaiser, O., Golyshin, P.N. Nat. Biotechnol. (2006) [Pubmed]
  5. The immunosuppressant drug FTY720 inhibits cytosolic phospholipase A2 independently of sphingosine-1-phosphate receptors. Payne, S.G., Oskeritzian, C.A., Griffiths, R., Subramanian, P., Barbour, S.E., Chalfant, C.E., Milstien, S., Spiegel, S. Blood (2007) [Pubmed]
  6. Apoptotic cells promote macrophage survival by releasing the antiapoptotic mediator sphingosine-1-phosphate. Weigert, A., Johann, A.M., von Knethen, A., Schmidt, H., Geisslinger, G., Brüne, B. Blood (2006) [Pubmed]
  7. 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]
  8. 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]
  9. 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]
  10. Positive modulation of IL-12 signaling by sphingosine kinase 2 associating with the IL-12 receptor beta 1 cytoplasmic region. Yoshimoto, T., Furuhata, M., Kamiya, S., Hisada, M., Miyaji, H., Magami, Y., Yamamoto, K., Fujiwara, H., Mizuguchi, J. J. Immunol. (2003) [Pubmed]
  11. The distribution of small and intermediate conductance calcium-activated potassium channels in the rat sensory nervous system. Mongan, L.C., Hill, M.J., Chen, M.X., Tate, S.N., Collins, S.D., Buckby, L., Grubb, B.D. Neuroscience (2005) [Pubmed]
  12. De novo biosynthesis of dihydrosphingosine-1-phosphate by sphingosine kinase 1 in mammalian cells. Berdyshev, E.V., Gorshkova, I.A., Usatyuk, P., Zhao, Y., Saatian, B., Hubbard, W., Natarajan, V. Cell. Signal. (2006) [Pubmed]
  13. 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]
  14. 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]
  15. Protein kinase D-mediated phosphorylation and nuclear export of sphingosine kinase 2. Ding, G., Sonoda, H., Yu, H., Kajimoto, T., Goparaju, S.K., Jahangeer, S., Okada, T., Nakamura, S. J. Biol. Chem. (2007) [Pubmed]
  16. Sphingosine kinase-2 inhibition improves mitochondrial function and survival after hepatic ischemia-reperfusion. Shi, Y., Rehman, H., Ramshesh, V.K., Schwartz, J., Liu, Q., Krishnasamy, Y., Zhang, X., Lemasters, J.J., Smith, C.D., Zhong, Z. J. Hepatol. (2012) [Pubmed]
  17. 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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