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A mutation in the second intracellular loop of the pituitary adenylate cyclase activating polypeptide type I receptor confers constitutive receptor activation
Author(s) -
Cao Yong-Jiang,
Gimpl Gerald,
Fahrenholz Falk
Publication year - 2000
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(00)01269-2
Subject(s) - enzyme linked receptor , 5 ht5a receptor , receptor , glucagon like peptide 1 receptor , growth hormone releasing hormone receptor , biology , adenylate kinase , secretin family , interleukin 21 receptor , microbiology and biotechnology , muscarinic acetylcholine receptor m5 , liver receptor homolog 1 , vasoactive intestinal peptide , biochemistry , chemistry , agonist , hormone receptor , neuropeptide , muscarinic acetylcholine receptor m3 , nuclear receptor , genetics , cancer , breast cancer , gene , transcription factor , acetylcholine receptor
The 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 G s proteins.