Functional role of carboxyl-terminal tail of prostaglandin EP3 receptor in Gi coupling.
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.
Hizaki
H
H
Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Hasegawa
H
H
Katoh
H
H
Negishi
M
M
Ichikawa
A
A
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000527:Alprostadil / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D007700:Kinetics; D007930:Leucine; D046911:Macromolecular Substances; D051379:Mice; D008961:Models, Structural; D016297:Mutagenesis, Site-Directed; D016133:Polymerase Chain Reaction; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology; D011487:Protein Conformation; D018078:Receptors, Prostaglandin E / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D058308:Receptors, Prostaglandin E, EP3 Subtype; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D017384:Sequence Deletion; D014162:Transfection; D014633:Valine
D046911:Macromolecular Substances; D011459:Prostaglandins E, Synthetic; C545648:Ptger3 protein, mouse; D018078:Receptors, Prostaglandin E; D058308:Receptors, Prostaglandin E, EP3 Subtype; D011994:Recombinant Proteins; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C032405:11-deoxy-16-phenoxy-17,18,19,20-tetranorprostaglandin E1; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D000527:Alprostadil; D007930:Leucine; D014633:Valine