Sphingosine, D-erythro

Common component of cell membranes, often as phosphatidyl conjugates. Is a potent (IC₅₀=1-3 µM) and selective inhibitor of protein kinase C. Inhibition is competitive with diacylglycerol, phorbol dibutyrate and Ca²⁺ and it also inhibits PKC activation by other lipids. It acts on an equimolar basis with 1,2-dioleoylglycerol and does not affect other kinases such as MLCK and PKA. It is active in intact cells and has been identified as an endogenous constituent in HL-60 cells, neutrophils, rat liver, and brain and mouse tissues. Other activities include inhibition of phosphatidate phosphohydrolase, Na⁺,K⁺-ATPase, CTP:phosphocholine cytidylyltransferase, calmodulin-dependent enzymes, binding of factor VII to tissue factor, binding of thyrotropin releasing hormone to its receptor and activation of EGF receptor kinase, phospholipase D and casein kinase II.