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Background
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Sphingosine Kinase (SphK) catalyzes the phosphorylation of the lipid sphingosine, creating the bioactive lipid sphingosine-1-phosphate (S1P). S1P subsequently signals through cell surface G protein-coupled receptors, as well as intracellularly, to modulate cell proliferation, survival, motility and differentiation. SphK is an important signaling enzyme which is activated by diverse agents, including growth factors that signal through receptor tyrosine kinases, agents activating G protein-coupled receptors, and immunoglobulin receptors. Two SphK isotypes, SphK-1 and SphK-2, have been cloned, and both isotypes are ubiquitously expressed. SphK-1 has been shown to mediate cell growth, prevention of apoptosis, and cellular transformation, and is upregulated in a variety of human tumors. In contrast, SphK-2 increases apoptosis, and may be responsible for phosphorylating and activating the immunosuppressive drug FTY720.
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Background
References
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- Ota, T., et al., Nat. Genet. 36(1):40-45 (2004).
- Nava, V.E., et al., FEBS Lett. 473(1):81-84 (2000).
- Melendez, A.J., et al., Gene 251(1):19-26 (2000).
- Pitson, S.M., et al., Biochem. J. 350 Pt 2, 429-441 (2000).
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