Sphingosine kinase 1 explained

Sphingosine kinase 1 is an enzyme that in humans is encoded by the SPHK1 gene.^{[1] [2]}

Sphingosine kinase 1 phosphorylates sphingosine to sphingosine-1-phosphate (S1P). SK1 is normally a cytosolic protein but is recruited to membranes rich in phosphatidate (PA), a product of phospholipase D (PLD).^[3]

Sphingosine-1-phosphate (S1P) is a novel lipid messenger with both intracellular and extracellular functions. Intracellularly, it regulates proliferation and survival, and extracellularly, it is a ligand for EDG1. Various stimuli increase cellular levels of S1P by activation of sphingosine kinase (SPHK), the enzyme that catalyzes the phosphorylation of sphingosine. Competitive inhibitors of SPHK block formation of S1P and selectively inhibit cellular proliferation induced by a variety of factors, including platelet-derived growth factor and serum.^[2]

Interactions

SPHK1 has been shown to interact with TRAF2.^[4]

Further reading

• Tsukahara T, Mizuno H, Igarashi Y . [Molecular diversity of sphingosine kinase] . Tanpakushitsu Kakusan Koso. Protein, Nucleic Acid, Enzyme . 47 . 4 Suppl . 509–13 . Mar 2002 . 11915350 .
• Sudo K, Chinen K, Nakamura Y . 2058 expressed sequence tags (ESTs) from a human fetal lung cDNA library . Genomics . 24 . 2 . 276–9 . Nov 1994 . 7698749 . 10.1006/geno.1994.1616 .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . Jan 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Hillier LD, Lennon G, Becker M, Bonaldo MF, Chiapelli B, Chissoe S, Dietrich N, DuBuque T, Favello A, Gish W, Hawkins M, Hultman M, Kucaba T, Lacy M, Le M, Le N, Mardis E, Moore B, Morris M, Parsons J, Prange C, Rifkin L, Rohlfing T, Schellenberg K, Bento Soares M, Tan F, Thierry-Meg J, Trevaskis E, Underwood K, Wohldman P, Waterston R, Wilson R, Marra M . Generation and analysis of 280,000 human expressed sequence tags . Genome Research . 6 . 9 . 807–28 . Sep 1996 . 8889549 . 10.1101/gr.6.9.807 . free .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . Oct 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Liu H, Sugiura M, Nava VE, Edsall LC, Kono K, Poulton S, Milstien S, Kohama T, Spiegel S . Molecular cloning and functional characterization of a novel mammalian sphingosine kinase type 2 isoform . The Journal of Biological Chemistry . 275 . 26 . 19513–20 . Jun 2000 . 10751414 . 10.1074/jbc.M002759200 . free .
• Nava VE, Lacana E, Poulton S, Liu H, Sugiura M, Kono K, Milstien S, Kohama T, Spiegel S . Functional characterization of human sphingosine kinase-1 . FEBS Letters . 473 . 1 . 81–4 . May 2000 . 10802064 . 10.1016/S0014-5793(00)01510-6 . 41144799 . free .
• Melendez AJ, Carlos-Dias E, Gosink M, Allen JM, Takacs L . Human sphingosine kinase: molecular cloning, functional characterization and tissue distribution . Gene . 251 . 1 . 19–26 . Jun 2000 . 10863092 . 10.1016/S0378-1119(00)00205-5 .
• Pitson SM, D'andrea RJ, Vandeleur L, Moretti PA, Xia P, Gamble JR, Vadas MA, Wattenberg BW . Human sphingosine kinase: purification, molecular cloning and characterization of the native and recombinant enzymes . The Biochemical Journal . 350 Pt 2 . 2. 429–41 . Sep 2000 . 10947957 . 1221270 . 10.1042/0264-6021:3500429 .
• Xia P, Wang L, Moretti PA, Albanese N, Chai F, Pitson SM, D'Andrea RJ, Gamble JR, Vadas MA . Sphingosine kinase interacts with TRAF2 and dissects tumor necrosis factor-alpha signaling . The Journal of Biological Chemistry . 277 . 10 . 7996–8003 . Mar 2002 . 11777919 . 10.1074/jbc.M111423200 . free .
• Hayashi S, Okada T, Igarashi N, Fujita T, Jahangeer S, Nakamura S . Identification and characterization of RPK118, a novel sphingosine kinase-1-binding protein . The Journal of Biological Chemistry . 277 . 36 . 33319–24 . Sep 2002 . 12077123 . 10.1074/jbc.M201442200 . free . 20.500.14094/D1002671 . free .
• Lacaná E, Maceyka M, Milstien S, Spiegel S . Cloning and characterization of a protein kinase A anchoring protein (AKAP)-related protein that interacts with and regulates sphingosine kinase 1 activity . The Journal of Biological Chemistry . 277 . 36 . 32947–53 . Sep 2002 . 12080051 . 10.1074/jbc.M202841200 . free .
• Johnson KR, Becker KP, Facchinetti MM, Hannun YA, Obeid LM . PKC-dependent activation of sphingosine kinase 1 and translocation to the plasma membrane. Extracellular release of sphingosine-1-phosphate induced by phorbol 12-myristate 13-acetate (PMA) . The Journal of Biological Chemistry . 277 . 38 . 35257–62 . Sep 2002 . 12124383 . 10.1074/jbc.M203033200 . free .
• Pitson SM, Moretti PA, Zebol JR, Zareie R, Derian CK, Darrow AL, Qi J, D'Andrea RJ, Bagley CJ, Vadas MA, Wattenberg BW . The nucleotide-binding site of human sphingosine kinase 1 . The Journal of Biological Chemistry . 277 . 51 . 49545–53 . Dec 2002 . 12393916 . 10.1074/jbc.M206687200 . free .
• Nava VE, Hobson JP, Murthy S, Milstien S, Spiegel S . Sphingosine kinase type 1 promotes estrogen-dependent tumorigenesis of breast cancer MCF-7 cells . Experimental Cell Research . 281 . 1 . 115–27 . Nov 2002 . 12441135 . 10.1006/excr.2002.5658 .
• MacKinnon AC, Buckley A, Chilvers ER, Rossi AG, Haslett C, Sethi T . Sphingosine kinase: a point of convergence in the action of diverse neutrophil priming agents . Journal of Immunology . 169 . 11 . 6394–400 . Dec 2002 . 12444147 . 10.4049/jimmunol.169.11.6394 . free .

External links

• Sphingosine kinase 1 . Paugh SW, Kapitonov D, Spiegel S . 2007-11-08 . UCSD Nature Molecule Pages . Signaling Gateway: University of California San Diego (UCSD) and Nature Publishing Group . 10.1038/mp.a002219.01 . 2008-09-15 . 2008-03-15 . https://web.archive.org/web/20080315105521/http://www.signaling-gateway.org/molecule/query?afcsid=A002219 . dead .

Notes and References

1. Kohama T, Olivera A, Edsall L, Nagiec MM, Dickson R, Spiegel S . Molecular cloning and functional characterization of murine sphingosine kinase . The Journal of Biological Chemistry . 273 . 37 . 23722–8 . Sep 1998 . 9726979 . 10.1074/jbc.273.37.23722 . free .
2. Web site: Entrez Gene: SPHK1 sphingosine kinase 1.
3. Delon C, Manifava M, Wood E, Thompson D, Krugmann S, Pyne S, Ktistakis NT. Sphingosine Kinase 1 Is an Intracellular Effector of Phosphatidic Acid. The Journal of Biological Chemistry. 279. 43. 44763–44774. 2004. 10.1074/jbc.M405771200. free. 15310762.
4. Xia P, Wang L, Moretti PA, Albanese N, Chai F, Pitson SM, D'Andrea RJ, Gamble JR, Vadas MA . Sphingosine kinase interacts with TRAF2 and dissects tumor necrosis factor-alpha signaling . The Journal of Biological Chemistry . 277 . 10 . 7996–8003 . Mar 2002 . 11777919 . 10.1074/jbc.M111423200 . free .