ACTIVATION OF MITOGEN-ACTIVATED PROTEIN-KINASE BY THE HUMAN PROSTAGLANDIN EP(3A) 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 E(2) (PGE(2)) which inhibits adenylyl cyclase and as been defined as the EP(3A) (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 EP(3A), I mu M PGE(2) stimulated MAP kinase activity similar to 1.3-fold with an EC(50) of similar to 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 EP(3A) receptor may explain the proliferative actions of PGE(2) in some tissues. (C) 1995 Academic Press, Inc.