Development of Our Current Understanding of Bioactive Lysophospholipids

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Abstract
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 Gα12/13‐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.