Saccharomyces contain two sphingoid long chain base kinases that define a new family of lipid kinases with the potential to regulate signal transduction pathways and lipid synthesis

Recent experiments with mammalian ceils have implicated sphingosine-1phosphate (SPP). a type of sphingolipid long chain base (LCB) phosphate, as a .second messenger for regulating ce!lula,r proliferation and a variety of other processes. SPP is catabolized by a conserved pathway to form phospholipid precursors. A sphingosine kinase has never been purified nor has any gene en coding such an enzyme been identified. A genetic selection procedure enabled us to identified two homologous Saccharomyces cerevisiae genes, LCB4 and LCB5, necessary for LCB kinase activity. Expression of either gene in Escherichia coli generates soluble LCB kina.se activity, demonstrating that each gene encodes enzyme activity. The Lcb4 and Lcb5 proteins are not related to any known protein and thus represent a new type of protein and a new type of lipid kinase. I he proteins are evolutionary conserved since mouse and human homologs exist. About half of the Lcb4 enzyme activity is soluble and the remainder is in the membrane fraction. Since neither Lcb protein has a putative domain for membrane binding, it is not clear if the enzymes are bound to a membrane or reside within an organelle. All eucaryotes that have been examined contain LCB kinase activity. Such conservation is consistent with essential function(s) including generation of second messengers and regulation of metabolic flux into phospholipid synthetic pathways. Studies of LCB kinase function, particularly in stress responses and phospholipid synthesis, will be discussed.