Signal transduction by sphingosine kinase

Abstract Several new findings in the last few years have drastically challenged our view of the role of sphingolipids in cellular function. It is now evident that not only the complex sphingolipids of the plasma membrane, but also small molecules of sphingolipid metabolism, play an essential role in cellular regulation. Analogous to the breakdown products of glycerophospholipids, certain small sphingolipids are messenger molecules which transduce information both between cells and within cells. Of these, ceramide and sphingosine-1- phosphate (SPP) have gained major attention (1), although others may also have a signalling function. Ceramide is cleaved from sphingomyelin by sphingomyelinase(s) (see Figure 1), and apparently plays an important role in apoptosis. SPP was originally considered as an intermediate product in the breakdown of sphingosine, but now it is recognized that it controls a variety of cellular functions.