Sphingosine-1-phosphate (SPP) 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 SPP by activation of sphingosine kinase (SPHK), the enzyme that catalyzes the phosphorylation of sphingosine. Competitive inhibitors of SPHK block formation of SPP and selectively inhibit cellular proliferation induced by a variety of factors, including platelet-derived growth factor and serum.Sequence comparisons of the mammalian SPHK proteins and SPHKs from other organisms identified 5 regions that are highly conserved. Northern blot analysis of mouse adult tissues showed ubiquitous expression of Sphk1, with the highest levels found in lung and spleen.