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Gene Review

Sphk1  -  sphingosine kinase 1

Rattus norvegicus

Synonyms: SK 1, SPK 1, Sphingosine kinase 1
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Disease relevance of Sphk1


High impact information on Sphk1


Biological context of Sphk1


Anatomical context of Sphk1

  • These results suggest that astrocyte lpR signalling mechanisms likely involve both Gi- and Gq-coupled GPCRs and that receptor-mediated activation of SK leads to intracellular generation of S1P, which in turn amplifies the lpR signalling in a paracrine/autocrine manner [1].
  • Therefore, we examined the expression of SK1 and COX-2 in rat colon tumors induced by azoxymethane (AOM) and the relationship of these two proteins in normal and malignant intestinal epithelial cells [2].
  • These results indicate that, in these cells, depletion of intracellular nonmitochondrial or mitochondrial Ca(2+) stores causes cell death, that TG activates phospholipase A(2) and sphingosine kinase, and that arachidonic acid induces neurite outgrowth, whereas S1P delays cell death [11].
  • Phorbol ester treatment resulted in an increase in sphingosine kinase 1 activity in the membranes, accompanied by a significant increase in extracellular S1P [12].
  • Novel role of sphingosine kinase 1 as a mediator of neurotrophin-3 action in oligodendrocyte progenitors [13].

Associations of Sphk1 with chemical compounds


Other interactions of Sphk1


Analytical, diagnostic and therapeutic context of Sphk1

  • The increase in SK1 and COX-2 expression in AOM-induced rat colon adenocarcinoma was confirmed at the level of mRNA by real-time RT-PCR [2].
  • Purified sphingosine kinase has an apparent molecular mass of approximately 49 kDa under denaturing conditions on SDS-polyacrylamide gel, which is similar to the molecular mass determined by gel filtration, suggesting that the active form is a monomer [10].


  1. Pharmacological characterization of lysophospholipid receptor signal transduction pathways in rat cerebrocortical astrocytes. Rao, T.S., Lariosa-Willingham, K.D., Lin, F.F., Palfreyman, E.L., Yu, N., Chun, J., Webb, M. Brain Res. (2003) [Pubmed]
  2. Sphingosine kinase 1 is up-regulated in colon carcinogenesis. Kawamori, T., Osta, W., Johnson, K.R., Pettus, B.J., Bielawski, J., Tanaka, T., Wargovich, M.J., Reddy, B.S., Hannun, Y.A., Obeid, L.M., Zhou, D. FASEB J. (2006) [Pubmed]
  3. Involvement of sphingosine 1-phosphate in nerve growth factor-mediated neuronal survival and differentiation. Edsall, L.C., Pirianov, G.G., Spiegel, S. J. Neurosci. (1997) [Pubmed]
  4. Regulatory role of sphingomyelin metabolites in hypoxia-induced vascular smooth muscle cell proliferation. Yun, J.K., Kester, M. Arch. Biochem. Biophys. (2002) [Pubmed]
  5. Differential transactivation of sphingosine-1-phosphate receptors modulates NGF-induced neurite extension. Toman, R.E., Payne, S.G., Watterson, K.R., Maceyka, M., Lee, N.H., Milstien, S., Bigbee, J.W., Spiegel, S. J. Cell Biol. (2004) [Pubmed]
  6. Expression of SphK1 impairs degranulation and motility of RBL-2H3 mast cells by desensitizing S1P receptors. Jolly, P.S., Bektas, M., Watterson, K.R., Sankala, H., Payne, S.G., Milstien, S., Spiegel, S. Blood (2005) [Pubmed]
  7. Prosaposin treatment induces PC12 entry in the S phase of the cell cycle and prevents apoptosis: activation of ERKs and sphingosine kinase. Misasi, R., Sorice, M., Di Marzio , L., Campana, W.M., Molinari, S., Cifone, M.G., Pavan, A., Pontieri, G.M., O'Brien, J.S. FASEB J. (2001) [Pubmed]
  8. Sphingosine kinase 1 is an intracellular effector of phosphatidic acid. Delon, C., Manifava, M., Wood, E., Thompson, D., Krugmann, S., Pyne, S., Ktistakis, N.T. J. Biol. Chem. (2004) [Pubmed]
  9. CpG island of rat sphingosine kinase-1 gene: tissue-dependent DNA methylation status and multiple alternative first exons. Imamura, T., Ohgane, J., Ito, S., Ogawa, T., Hattori, N., Tanaka, S., Shiota, K. Genomics (2001) [Pubmed]
  10. Purification and characterization of rat kidney sphingosine kinase. Olivera, A., Kohama, T., Tu, Z., Milstien, S., Spiegel, S. J. Biol. Chem. (1998) [Pubmed]
  11. Distinct effects of different calcium-mobilizing agents on cell death in NG108-15 neuroblastoma X glioma cells. Chin, T.Y., Hwang, H.M., Chueh, S.H. Mol. Pharmacol. (2002) [Pubmed]
  12. Extracellular release of newly synthesized sphingosine-1-phosphate by cerebellar granule cells and astrocytes. Anelli, V., Bassi, R., Tettamanti, G., Viani, P., Riboni, L. J. Neurochem. (2005) [Pubmed]
  13. Novel role of sphingosine kinase 1 as a mediator of neurotrophin-3 action in oligodendrocyte progenitors. Saini, H.S., Coelho, R.P., Goparaju, S.K., Jolly, P.S., Maceyka, M., Spiegel, S., Sato-Bigbee, C. J. Neurochem. (2005) [Pubmed]
  14. S1P and LPA trigger Schwann cell actin changes and migration. Barber, S.C., Mellor, H., Gampel, A., Scolding, N.J. Eur. J. Neurosci. (2004) [Pubmed]
  15. Flavone acetic acid induces a G2/M cell cycle arrest in mammary carcinoma cells. Panaro, N.J., Popescu, N.C., Harris, S.R., Thorgeirsson, U.P. Br. J. Cancer (1999) [Pubmed]
  16. Depolarisation induces rapid and transient formation of intracellular sphingosine-1-phosphate. Alemany, R., Kleuser, B., Ruwisch, L., Danneberg, K., Lass, H., Hashemi, R., Spiegel, S., Jakobs, K.H., Meyer zu Heringdorf, D. FEBS Lett. (2001) [Pubmed]
  17. Sphingosine 1-phosphate induces expression of early growth response-1 and fibroblast growth factor-2 through mechanism involving extracellular signal-regulated kinase in astroglial cells. Sato, K., Ishikawa, K., Ui, M., Okajima, F. Brain Res. Mol. Brain Res. (1999) [Pubmed]
  18. Possible involvement of cell surface receptors in sphingosine 1-phosphate-induced activation of extracellular signal-regulated kinase in C6 glioma cells. Sato, K., Tomura, H., Igarashi, Y., Ui, M., Okajima, F. Mol. Pharmacol. (1999) [Pubmed]
  19. Essential requirement for sphingosine kinase activity in eNOS-dependent NO release and vasorelaxation. Roviezzo, F., Bucci, M., Delisle, C., Brancaleone, V., Di Lorenzo, A., Mayo, I.P., Fiorucci, S., Fontana, A., Gratton, J.P., Cirino, G. FASEB J. (2006) [Pubmed]
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