Third isoform of the prostaglandin‐E‐receptor EP3 subtype with different C‐terminal tail coupling to both stimulation and inhibition of adenylate cyclase

Abstract

A functional cDNA clone for a third isoform of the mouse prostaglandin‐E‐receptor EP3 subtype, derived by alternative RNA splicing, named the EP3γ receptor, was obtained in addition to those for the two other isoforms, EP3α and EP3β. The three isoforms are only different in the amino acid sequence of the putative cytoplasmic carboxy‐terminal tail. When expressed, EP3γ shows identical ligand‐binding properties to these of the other isoforms. The EP3‐selective agonist, M&B 28767, increased the basal cAMP level and inhibited the forskolin‐induced increase in the cAMP level in EP3γ, while it decreased both the basal and forskolin‐elevated cAMP levels in EP3α and EP3β. The M&B 28767‐stimulated GTPase activity consisted of pertussis‐toxin‐sensitive and cholera‐toxin‐sensitive portions in the EP3γ‐expressing cell membrane, suggested that EP3γ is coupled to both guanine nucleotide‐binding inhibitory and stimulatory proteins. These results indicate that EP3γ is coupled to both stimulation and inhibition of adenylate cyclase, but that EP3α and EP3β are exclusively coupled to inhibition of adenylate cyclase. Thus, alternative splicing produces a third isoform with a different carboxy‐terminal tail, which differs from the other two isoforms in the specificity of coupling to a signal‐transduction pathway. Copyright © 1993, Wiley Blackwell. All rights reserved