2 ISOFORMS OF PROSTAGLANDIN EP3 RECEPTOR EXHIBITING CONSTITUTIVE ACTIVITY AND AGONIST-DEPENDENT ACTIVITY IN RHO-MEDIATED STRESS FIBER FORMATION

We have cloned two isoforms of the mouse prostaglandin E receptor EP3 subtype, EP3 alpha and EP3 beta, with different carboxyl-terminal tail s, produced through alternative splicing. To determine the functional differences between the two isoforms, we examined the role of the isof orms in regulation of the actin cytoskeleton using Mardin-Darby canine kidney cells expressing these isoforms. The EP3 alpha isoform constit utively induced stress fiber formation, independent of an agonist, whi le the EP3 beta isoform agonist-dependently induced stress fiber forma tion. Pertussis toxin did not prevent stress fiber formation. This sig naling pathway is mediated by Rho, because C3 transferase microinjecti on inhibited stress fiber formation. Therefore, the physiological sign ificance of these isoforms of the EP3 receptor may lie in their differ ent agonist dependency in Rho-mediated stress fiber formation via a pe rtussis toxin-insensitive G protein. (C) 1997 Academic Press.