Functional role of carboxyl-terminal tail of prostaglandin EP3 receptor in Gi coupling

• Published in: FEBS letters Vol. 414; no. 2; p. 323
• Main Authors: Hizaki, H, Hasegawa, H, Katoh, H, Negishi, M, Ichikawa, A
• Format: Journal Article
• Language: English
• Published: England 08.09.1997
• Subjects: Adenylyl Cyclases - metabolism; Alprostadil - analogs & derivatives; Alprostadil - pharmacology; Animals; CHO Cells; Cricetinae; Cyclic AMP - metabolism; GTP-Binding Proteins - metabolism; Guanosine 5'-O-(3-Thiotriphosphate) - pharmacology; Kinetics; Leucine; Macromolecular Substances; Mice; Models, Structural; Mutagenesis, Site-Directed; Polymerase Chain Reaction; Prostaglandins E, Synthetic - pharmacology; Protein Conformation; Receptors, Prostaglandin E - chemistry; Receptors, Prostaglandin E - metabolism; Receptors, Prostaglandin E - physiology; Receptors, Prostaglandin E, EP3 Subtype; Recombinant Proteins - chemistry; Recombinant Proteins - metabolism; Sequence Deletion; Transfection; Valine
• ISSN: 0014-5793
• DOI: 10.1016/S0014-5793(97)01020-X

We recently demonstrated that the mouse EP3beta receptor and its carboxyl-terminal tail-truncated receptor showed agonist-dependent and full constitutive Gi activities, respectively (Hasegawa, H., Negishi, M. and Ichikawa, A. (1996) J. Biol. Chem. 271, 1857-1860). To assess the role of the carboxyl-terminal tail in the EP3beta receptor Gi coupling, we constructed a series of mutant receptors with progressively truncated carboxyl-termini. The truncated receptors displayed constitutive Gi activities, the degree of constitutive activity basically correlating with the inverse of the length of the carboxyl-terminal tail, but the sequence between Leu340 and Val347 was mainly contributed to the constitutive activity. Thus, the carboxyl-terminal tail plays an important role in the constraint of the EP3 receptor in its inactive conformation.