Activation of mitogen-activated protein kinase by the human prostaglandin EP3A receptor.
Mitogen-activated protein (MAP) kinases are involved with cellular proliferation, and while the traditional activators of these kinases have been the growth factor receptors, recent data indicate that G-protein coupled receptors which inhibit adenylyl cyclase can activate MAP kinases as well. We have recently cloned an alternative splice variant of a human receptor for prostaglandin E2 (PGE2) which inhibits adenylyl cyclase and as been defined as the EP3A (Brit. J. Pharmacol. 112:377, 1994). In the present study the ability of this receptor to activate MAP kinase was examined. In crude lysates of COS-7 cells transfected with the human EP3A, 1 microM PGE2 stimulated MAP kinase activity approximately 1.3-fold with an EC50 of approximately 6 nM. Ion exchange chromatography followed by immunoblot analysis showed that the stimulation of MAP kinase activity co-fractionated with immunoreactive MAP-2 kinase (ERK1). This activation of MAP kinase activity by the EP3A receptor may explain the proliferative actions of PGE2 in some tissues.
Burkey
T H
TH
Department of Pharmacology and Toxicology, College of Pharmacy/University of Arizona, Tucson 85721, USA.
Regan
J W
JW
D000704:Analysis of Variance; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000302:isolation & purification / Q000378:metabolism*; D002460:Cell Line; D002522:Chlorocebus aethiops; D015232:Dinoprostone / Q000494:pharmacology*; D004789:Enzyme Activation; D006801:Humans; D007668:Kidney; D007700:Kinetics; D010750:Phosphoproteins / Q000302:isolation & purification / Q000378:metabolism; D018078:Receptors, Prostaglandin E / Q000096:biosynthesis / Q000502:physiology*; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058308:Receptors, Prostaglandin E, EP3 Subtype; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D014162:Transfection
C545644:PTGER2 protein, human; C545647:PTGER3 protein, human; D010750:Phosphoproteins; D018078:Receptors, Prostaglandin E; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058308:Receptors, Prostaglandin E, EP3 Subtype; D011994:Recombinant Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D015232:Dinoprostone