  Sphingosine-1-phosphate: extracellular mediator or
intracellular second messenger?  Sphingosine-1-phosphate (SPP),
a polar sphingolipid metabolite, has received much attention
recently as an extracellular mediator and an intracellular
second messenger. It regulates a wide range of biological
responses such as cell growth, death, differentiation, and
migration. Recent identification of plasma membrane receptors
and the cloning of SPP metabolizing enzymes have increased our
understanding of the biology of SPP synthesis and action.
However, controversy exists regarding the mode of action of this
molecule. EDG-1 and related G-protein-coupled receptors were
identified recently as plasma membrane receptors for SPP. In
light of this recent discovery, many of the functions of SPP
previously thought to be due to intracellular second messenger
action should be reevaluated. In addition, signaling properties
and functions of the three known receptors for SPP need to be
fully delineated. The structures and the evolution