Development of Our Current Understanding of Bioactive Lysophospholipids



    Corresponding author
    1. Division of Cellular Biochemistry, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
      Corresponding author. Voice: +31–20-512 1971; fax: +31–20-512 1989.
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Corresponding author. Voice: +31–20-512 1971; fax: +31–20-512 1989.


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.