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Oncogene. 2001 Mar 26;20(13):1540-6.

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

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Division of Cellular Biochemistry, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.


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.

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