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.