Ras-MAP kinase signaling by lysophosphatidic acid and other G protein-coupled receptor agonists

Oncogene. 2001 Mar 26;20(13):1540-6. doi: 10.1038/sj.onc.1204187.


Lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) are extracellular lipid mediators that signal through distinct members of the Edg/LP subfamily of G protein-coupled receptors (GPCRs). LPA and S1P receptors are expressed in almost every cell type and can couple to multiple G proteins (G(i), G(q) and G(12/13)) to mediate a great variety of responses, ranging from rapid morphological changes to long-term stimulation of cell proliferation. LPA serves as the prototypic GPCR agonist that activates the small GTPases Ras (via G(i)) and RhoA (via G(12/13)), leading to activation of the mitogen-activated protein kinase (MAPK) cascade and reorganization of the actin cytoskeleton, respectively. This review focuses on our current insights into how Ras-MAPK signaling is regulated by GPCR agonists in general, and by LPA in particular.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Lysophospholipids / pharmacology*
  • MAP Kinase Signaling System*
  • Membrane Microdomains
  • Phosphatidylinositol 3-Kinases
  • Receptors, Cell Surface / agonists*
  • Receptors, Cell Surface / metabolism
  • Receptors, G-Protein-Coupled*
  • Receptors, Lysophosphatidic Acid
  • Receptors, Lysophospholipid
  • Sphingosine / analogs & derivatives*
  • Sphingosine / pharmacology*
  • ras Proteins / metabolism*


  • Lysophospholipids
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled
  • Receptors, Lysophosphatidic Acid
  • Receptors, Lysophospholipid
  • sphingosine 1-phosphate
  • Phosphatidylinositol 3-Kinases
  • ras Proteins
  • Sphingosine