Potentiation of G-protein-coupled receptor-induced MAP kinase activation by exogenous EGF receptors in SK-N-MC neuroepithelioma cells.
Lysophosphatidic acid (LPA) and endothelin-1 (ET-1), two ligands for G-protein coupled receptors (GPCRs), induce activation of mitogen activated protein kinase (MAPK). Surprisingly, LPA and ET-1 did not induce MAPK activation in SK-N-MC neuroepithelioma cells, even though these GPCR ligands evoked a rapid, transient rise in intracellular free Ca2+ concentration in these cells, indicating that SK-N-MC cells express functional LPA- and ET-1-receptors. Transient transfection of the EGFR into SK-N-MC cells, which do not express endogenous EGFR, potentiated LPA- and ET-1-induced MAPK activation. LPA and ET-1 did not enhance basal level tyrosine phosphorylation of the transfected EGFR in SK-N-MC cells. Even though the mechanism of LPA- and ET-1-induced MAPK activation in EGFR-transfected SK-N-MC cells remains to be determined definitively, our results provide strong evidence that the EGFR links these GPCRs to MAPK activation.
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Hubrecht Laboratory, Netherlands Institute for Developmental Biology, Uppsalalaan 8, Utrecht, 3584 CT, The Netherlands.
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den Hertog
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D000818:Animals; D019556:COS Cells; D002118:Calcium / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D004357:Drug Synergism; D019332:Endothelin-1 / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D066246:ErbB Receptors / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008246:Lysophospholipids / Q000378:metabolism; D018241:Neuroectodermal Tumors, Primitive, Peripheral / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000502:physiology*; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
D019332:Endothelin-1; D008246:Lysophospholipids; D011956:Receptors, Cell Surface; D066246:ErbB Receptors; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019204:GTP-Binding Proteins; D002118:Calcium