PT - JOURNAL ARTICLE AU - Hiromichi Fujino AU - Dinesh Srinivasan AU - Kristen L. Pierce AU - John W. Regan TI - Differential Regulation of Prostaglandin F<sub>2α</sub>Receptor Isoforms by Protein Kinase C DP - 2000 Feb 01 TA - Molecular Pharmacology PG - 353--358 VI - 57 IP - 2 4099 - http://molpharm.aspetjournals.org/content/57/2/353.short 4100 - http://molpharm.aspetjournals.org/content/57/2/353.full SO - Mol Pharmacol2000 Feb 01; 57 AB - Prostaglandin F2α receptors (FP) are G protein-coupled receptors that bind prostaglandin F2α(PGF2α), resulting in the activation of an inositol phosphate (IP) second messenger pathway. Alternative mRNA splicing generates two FP receptor isoforms. These isoforms, designated FPA and FPB, are otherwise identical except for their carboxyl termini. FPB is essentially a truncated version of FPA that lacks the 46 carboxyl-terminal amino acids, including four putative protein kinase C (PKC) phosphorylation sites. Until now, functional differences between these FP receptor isoforms have not been identified. We now report that pretreatment with the PKC inhibitor bisindolylmaleimide I enhanced PGF2α-stimulated IP accumulation in transfected cells stably expressing the FPA isoform but not in cells stably expressing the FPB isoform. Whole-cell phosphorylation experiments showed a strong agonist-dependent phosphorylation of the FPA isoform but little or no phosphorylation of the FPB. Pretreatment of cells with bisindolylmaleimide I decreased PGF2α-stimulated phosphorylation of the FPA isoform consistent with a PKC-dependent phosphorylation. In vitro phosphorylation of an FPAcarboxyl-terminal fusion protein by recombinant PKCα showed that the carboxyl terminus of the FPA is a substrate for PKC. These results suggest that PKC-dependent phosphorylation is responsible for differential regulation of second messenger signaling by FP prostanoid receptor isoforms. The American Society for Pharmacology and Experimental Therapeutics