Ras-MAP kinase signaling by lysophosphatidic acid and other G protein-coupled receptor agonists.
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.
Kranenburg
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Division of Cellular Biochemistry, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
Moolenaar
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WH
D008246:Lysophospholipids / Q000494:pharmacology*; D020935:MAP Kinase Signaling System; D021962:Membrane Microdomains; D019869:Phosphatidylinositol 3-Kinases; D011956:Receptors, Cell Surface / Q000819:agonists* / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D049368:Receptors, Lysophosphatidic Acid; D049312:Receptors, Lysophospholipid; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D018631:ras Proteins / Q000378:metabolism*
D008246:Lysophospholipids; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D049368:Receptors, Lysophosphatidic Acid; D049312:Receptors, Lysophospholipid; C060506:sphingosine 1-phosphate; D019869:Phosphatidylinositol 3-Kinases; D018631:ras Proteins; D013110:Sphingosine