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 activ ated protein kinase (MAPK). Surprisingly, LPA and ET-1 did not induce MAPK activation in SK-N-MC neuroepithelioma cells, even though these G PCR ligands evoked a rapid, transient rise in intracellular free Ca2concentration in these cells, indicating that SK-N-MC cells express fu nctional LPA- and ET-1-receptors. Transient transfection of the EGFR i nto SK-N-MC cells, which do not express endogenous EGFR, potentiated L PA- and ET-1-induced MAPK activation. LPA and ET-1 did not enhance bas al level tyrosine phosphorylation of the transfected EGFR in SK-N-MC c ells. Even though the mechanism of LPA- and ET-1-induced MAPK activati on in EGFR-transfected SK-N-MC cells remains to be determined definiti vely, our results provide strong evidence that the EGFR links these GP CRs to MAPK activation. (C) 1998 Academic Press.