Sphingolipid metabolites and the cellular phenotype

Abstract

Sphingolipids are complex ubiquitous lipids that have been relegated to serving a structural role in membranes. Over the last few years, sphingolipid derivatives have been identified as intracellular signal transducing molecules (1-3). Sequential catabolic metabolites of sphingomyelin induce opposing biological effects; ceramides suppress mitogenesis and sphingosines enhance cell growth. The intracellular signaling pathways transducing these effects currently remain elusive. In this review, I will focus upon recent advances in the field of sphingolipid signaling with particular emphasis on the regulation of intracellular kinase cascades by sphingolipid-derived second messengers. Selective activation of distinct mitogen-activated protein kinase (MAPK) cascades by sphingolipid metabolites may, in part, determine the cellular phenotype.