Lipid biochemistry: functions of glycerolipids and sphingolipids in cellular signaling

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Abstract
Products of glycerolipid and sphingolipid metabolism are now known to fulfill second messenger functions in a variety of cellular signaling pathways. Evidence for glycerolipid-derived second messengers was first obtained from the "phosphatidylinositol cycle," which involves a signal-dependent hydrolysis of phosphatidylinositol bisphosphate yielding diacylglycerol and inositol trisphosphate. The role of diacylglycerol in the regulation of protein kinase C activity and its site of interaction with PKC are now well known. Recently, another glycerolipid second messenger, phosphatidic acid, was found to interact with the protooncogenic Raf-1 kinase. In cultured cells, a signal-induced generation of phosphatidic acid was critical for Raf-1 translocation to the cell membrane. Thus, different glycerolipid second messengers appear to regulate distinct targets with exquisite specificity. Analogous to the PI cycle, a "sphingomyelin cycle" was also found to exist, generating sphingolipid second messengers. Ceramide, ...

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