Journal
ONCOGENE
Volume 20, Issue 13, Pages 1540-1546Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.onc.1204187
Keywords
lysophosphatidic acid; sphingosine-1-phosphate; G protein coupled receptors; Ras; Rho; MAP kinase
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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 Pas (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.
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