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A role for K268 in V2R folding
Author(s) -
Gouill Christian Le,
Darden Thomas,
Madziva Michael T.,
Birnbaumer Mariel
Publication year - 2005
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/j.febslet.2005.08.003
Subject(s) - g protein coupled receptor , chemistry , amino acid , arginine , biochemistry , ligand (biochemistry) , internalization , mutant , vasopressin receptor , receptor , microbiology and biotechnology , biology , gene
The V2 vasopressin receptor, a member of the rhodopsin subfamily of GPCRs, mediates arginine vasopressin control of water reabsorption in the kidney by activating Gs. Requirement of the third intracellular loop of the V2R for G s activation was identified by introducing V2R segments into the Gq coupled V1aR [Liu, J. and Wess, J. (1996) J. Biol. Chem. 271, 8772–8778]; the same approach recognized glutamate 231 and glutamine 225 at the amino terminus of loop 3i as being needed for signal transduction. Site‐directed mutagenesis of the V2R confirmed their observations. Recently, we found that a positively charged amino acid at codon 268 is essential for V2R expression, although a double‐mutant bearing lysine at position 231 and glutamic acid at position 268 was expressed at higher levels than the wild type V2R and displayed unchanged ligand‐binding affinity. Ligand‐induced internalization and phosphorylation of the double‐mutant receptor was indistinguishable from that observed with the wild type protein but signaling activity was greatly diminished. The data suggested these two amino acids might interact with each other and might play a role in promoting GDP/GTP exchange.