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Am J Physiol Cell Physiol 286: C798-C806, 2004. First published November 26, 2003; doi:10.1152/ajpcell.00465.2003
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RECEPTORS AND SIGNAL TRANSDUCTION

Contribution of PKC-dependent and -independent processes in temporal ERK regulation by ET-1, PDGF, and EGF in rat myometrial cells

Philippe Robin, Isaline Boulven, Christine Bôle-Feysot, Zahra Tanfin, and Denis Leiber

Laboratoire de Signalisation et Régulations Cellulaires, Centre National de la Recherche Scientifique Unité Mixte de Recherche 8619, IFR 46, Université de Paris-Sud, 91405 Orsay Cedex, France

Submitted 24 October 2003 ; accepted in final form 20 November 2003

Endothelin-1 (ET-1), platelet-derived growth factor (PDGF), and epidermal growth factor (EGF) stimulated thymidine incorporation with different efficiency (PDGF >> EGF = ET-1) in rat myometrial cells. They also stimulated ERK activation, which culminated at 5 min and then declined to reach a plateau (at 45 min: EGF > 90%, PDGF = 50%, and ET-1 < 10% of maximum). Inhibition and downregulation of PKC demonstrated that ERK activation at 5 min involved PKC{delta} and -{zeta} for ET-1 and PKC{alpha} plus another PKC isoform for PDGF. By contrast, the EGF response did not involve PKC. Stimulation of Ras was more important with EGF than with PDGF, with ET-1 being the weakest activator. The simultaneous incubation of the cells with EGF and ET-1 potentiated the ERK activation at 5 min and mimicked the plateau phase obtained with PDGF. Under these conditions thymidine incorporation was comparable to that induced by PDGF. Taken together, our results indicated that the kinetic profile of ERK activation and its impact on cell proliferation can be modulated by the differential involvement of PKC isoforms and the amplitude of Ras activation.

uterine smooth muscle; phospholipase C; ETA receptor; thymidine incorporation; Ras



Address for reprint requests and other correspondence: P. Robin, Laboratoire de Signalisation et Régulations Cellulaires, CNRS UMR 8619, Bâtiment 430, Université de Paris-Sud, 91405 Orsay Cedex, France (E-mail: philippe.robin{at}bbmpc.u-psud.fr).




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