A mutation in the second intracellular loop of the pituitary adenylate cyclase activating polypeptide type I receptor confers constitutive receptor activation

6533b857fe1ef96bd12b46a0

RESEARCH PRODUCT

A mutation in the second intracellular loop of the pituitary adenylate cyclase activating polypeptide type I receptor confers constitutive receptor activation

Yong-jiang Cao Falk Fahrenholz Gerald Gimpl

subject

endocrine system Growth-hormone-releasing hormone receptor Molecular Sequence Data Receptors Pituitary Adenylate Cyclase-Activating Polypeptide Biophysics Glutamic Acid Signal transduction Transfection Biochemistry Beta-1 adrenergic receptor Constitutive activity Structural Biology cAMP Cyclic AMP Genetics Enzyme-linked receptor Animals 5-HT5A receptor Amino Acid Sequence Receptors Pituitary Hormone Molecular Biology Sequence Deletion Peptide hormone receptor Site-directed mutagenesis Pituitary adenylate cyclase activating polypeptide Chemistry Liver receptor homolog-1 Cell Biology Molecular biology Rats Interleukin-21 receptor COS Cells Mutagenesis Site-Directed Estrogen-related receptor gamma Sequence Alignment Glucagon receptor family hormones hormone substitutes and hormone antagonists Adenylyl Cyclases Receptors Pituitary Adenylate Cyclase-Activating Polypeptide Type I

description

AbstractThe pituitary adenylate cyclase activating polypeptide (PACAP) type I receptor belongs to the glucagon/secretin/vasoactive intestinal polypeptide (VIP) receptor family. We mutated and deleted an amino acid residue (E261) which is located within the second intracellular loop of the rat PACAP type I receptor and which is highly conserved among the receptor family. The wild-type receptor and the mutant receptors were efficiently expressed at the surface of COS-7 cells at nearly the same level and revealed the same high affinity for the agonist PACAP-27. The cAMP contents of COS cells transfected with the E261A, E261Q, and the deletion mutant receptor were 4.6-, 5.7-, and 6.7-fold higher as compared with COS cells transfected with the wild-type receptor. Thus, all the mutant PACAP receptors were constitutively active. The data suggest that the glutamic acid in the second intracellular loop of the PACAP receptor may be a key residue to constrain the receptor in the inactive conformation with respect to its coupling to Gs proteins.

year	journal	country	edition	language
2000-03-08	FEBS Letters

https://doi.org/10.1016/s0014-5793(00)01269-2