Differential regulation of prostaglandin receptor isoforms by protein kinase C

Hiromichi Fujino, Dinesh Srinivasan, Kristen L. Pierce, John W Regan

Research output: Contribution to journalArticle

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Abstract

Prostaglandin F(2α) receptors (FP) are G protein-coupled receptors that bind prostaglandin F(2α) (PGF(2α)), resulting in the activation of an inositol phosphate (IP) second messenger pathway. Alternative mRNA splicing generates two FP receptor isoforms. These isoforms, designated FP(A) and FP(B), are otherwise identical except for their carboxyl termini. FP(B) is essentially a truncated version of FP(A) 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 PGF(2α)-stimulated IP accumulation in transfected cells stably expressing the FP(A) isoform but not in cells stably expressing the FP(B) isoform. Whole-cell phosphorylation experiments showed a strong agonist-dependent phosphorylation of the FP(A) isoform but little or no phosphorylation of the FP(B). Pretreatment of cells with bisindolylmaleimide I decreased PGF(2α)-stimulated phosphorylation of the FP(A) isoform consistent with a PKC-dependent phosphorylation. In vitro phosphorylation of an FP(A) carboxyl-terminal fusion protein by recombinant PKCα showed that the carboxyl terminus of the FP(A) 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.

Original languageEnglish (US)
Pages (from-to)353-358
Number of pages6
JournalMolecular Pharmacology
Volume57
Issue number2
StatePublished - 2000

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Prostaglandin Receptors
Protein Kinase C
Protein Isoforms
Phosphorylation
Prostaglandins F
Second Messenger Systems
Inositol Phosphates
Protein C Inhibitor
Alternative Splicing
Protein Kinase Inhibitors
G-Protein-Coupled Receptors
Recombinant Proteins
Amino Acids
Messenger RNA
prostaglandin F2alpha receptor

ASJC Scopus subject areas

  • Pharmacology

Cite this

Differential regulation of prostaglandin receptor isoforms by protein kinase C. / Fujino, Hiromichi; Srinivasan, Dinesh; Pierce, Kristen L.; Regan, John W.

In: Molecular Pharmacology, Vol. 57, No. 2, 2000, p. 353-358.

Research output: Contribution to journalArticle

Fujino, H, Srinivasan, D, Pierce, KL & Regan, JW 2000, 'Differential regulation of prostaglandin receptor isoforms by protein kinase C', Molecular Pharmacology, vol. 57, no. 2, pp. 353-358.
Fujino, Hiromichi ; Srinivasan, Dinesh ; Pierce, Kristen L. ; Regan, John W. / Differential regulation of prostaglandin receptor isoforms by protein kinase C. In: Molecular Pharmacology. 2000 ; Vol. 57, No. 2. pp. 353-358.
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