Sphingolipids are metabolized into bioactive products that include ceramide, sphingosine, and sphingosine-1-phosphate (S1P). Sphingosine Kinase (SK) catalyzes the phosphorylation of the lipid sphingosine, creating S1P. S1P subsequently signals through cell surface G protein-coupled receptors, as well as intracellularly, to modulate cell proliferation, survival, motility and differentiation. Two isoforms of SK have been identified, SK1 and SK2. The mRNA for both of these isoforms is widely expressed with SK1 expression highest in brain, heart, kidney, thymus, spleen and lung, while SK2 is highest in kidney and liver. SKs can be activated through growth factor, G protein-coupled, and immunoglobulin receptor signalling. SK1 has been shown to mediate cell growth, prevention of apoptosis, and cellular transformation, and is upregulated in a variety of human tumors. Regulation of SK1 may occur through ERK mediated phosphorylation of Ser-225. This phosphorylation leads to increased activity and translocation to the plasma membrane.
