Development of our current understanding of bioactive lysophospholipids

Lysophosphatidic acid (LPA) serves as the prototypic lysophospholipid mediator that acts through G-protein-coupled receptors to evoke a host of responses in numerous target cells. The hormone- and growth-factor-like activities of LPA, mediated by distinct G proteins, were discovered about 10 years ago. Since then, considerable progress has been made in our understanding of LPA receptor signaling, culminating in the recent identification of a growing family of heptahelical receptors specific for LPA and the structurally related lysolipid, sphingosine-1-phosphate (S1P). In addition to stimulating Gi-Ras-mediated cell proliferation, LPA and S1P induce rapid G alpha 12/13-RhoA-mediated cytoskeletal changes underlying such diverse responses as neurite retraction, cell rounding, and enhanced tumor cell invasiveness. LPA also triggers inhibition of gap-junctional communication. This overview focuses on how our understanding of LPA as an intercellular lipid mediator has developed during the last decade.