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]
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Nava VE, Lacana E, Poulton S, Liu H, Sugiura M, Kono K, Milstien S, Kohama T, Spiegel S (May 2000). "Functional characterization of human sphingosine kinase-1". FEBS Letters. 473 (1): 81–4. doi:10.1016/S0014-5793(00)01510-6. PMID10802064.
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Hayashi S, Okada T, Igarashi N, Fujita T, Jahangeer S, Nakamura S (Sep 2002). "Identification and characterization of RPK118, a novel sphingosine kinase-1-binding protein". The Journal of Biological Chemistry. 277 (36): 33319–24. doi:10.1074/jbc.M201442200. PMID12077123.
Lacaná E, Maceyka M, Milstien S, Spiegel S (Sep 2002). "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. doi:10.1074/jbc.M202841200. PMID12080051.
Johnson KR, Becker KP, Facchinetti MM, Hannun YA, Obeid LM (Sep 2002). "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. doi:10.1074/jbc.M203033200. PMID12124383.
Pitson SM, Moretti PA, Zebol JR, Zareie R, Derian CK, Darrow AL, Qi J, D'Andrea RJ, Bagley CJ, Vadas MA, Wattenberg BW (Dec 2002). "The nucleotide-binding site of human sphingosine kinase 1". The Journal of Biological Chemistry. 277 (51): 49545–53. doi:10.1074/jbc.M206687200. PMID12393916.
Nava VE, Hobson JP, Murthy S, Milstien S, Spiegel S (Nov 2002). "Sphingosine kinase type 1 promotes estrogen-dependent tumorigenesis of breast cancer MCF-7 cells". Experimental Cell Research. 281 (1): 115–27. doi:10.1006/excr.2002.5658. PMID12441135.
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External links
Paugh SW, Kapitonov D, Spiegel S (2007-11-08). "Sphingosine kinase 1". UCSD-Nature Molecule Pages. Signaling Gateway: University of California San Diego (UCSD) and Nature Publishing Group. doi:10.1038/mp.a002219.01. Retrieved 2008-09-15.