SPHINGOSINE-1-PHOSPHATE AS 2ND MESSENGER IN CELL-PROLIFERATION INDUCED BY PDGF AND FCS MITOGENS

GROWTH signalling networks that use glycerophospholipid metabolites as second messengers have been well characterized1,2, but less is known of the second messengers derived from sphingolipids3,4, another major class of membrane lipids. A tantalizing fink between sphingolipids and cellular proliferation has emerged from the discovery that the sphingolipid metabolites sphingosine and sphingosine-1-phosphate stimulate growth of quiescent Swiss 3T3 fibroblasts by a pathway that is independent of protein kinase C5,6. Sphingosine-1-phosphate is rapidly produced from sphingosine and may mediate its biological effects6. Furthermore, sphingosine-1-phosphate triggers the dual signal transduction pathways of calcium mobilization6,7 and activation of phospholipase D8, prominent events in the control of cellular proliferation. Here we report that activation of sphingosine kinase and the formation of sphingosine-1-phosphate are important in the signal transduction pathways activated by the potent mitogens platelet-derived growth factor (PDGF) and fetal calf serum (FCS).