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

FEBS Lett. 1997 Sep 8;414(2):323-6. doi: 10.1016/s0014-5793(97)01020-x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

  • Macromolecular Substances
  • Prostaglandins E, Synthetic
  • Ptger3 protein, mouse
  • Receptors, Prostaglandin E
  • Receptors, Prostaglandin E, EP3 Subtype
  • Recombinant Proteins
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • 11-deoxy-16-phenoxy-17,18,19,20-tetranorprostaglandin E1
  • Cyclic AMP
  • GTP-Binding Proteins
  • Adenylyl Cyclases
  • Alprostadil
  • Leucine
  • Valine