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• W2113756625 startingPage "281" @default.
• W2113756625 abstract "The human B1 bradykinin (BK) receptor (B1R) is more efficacious than the human B2 BK receptor (B2R) in both ligand-independent and agonist-dependent coupling to G_q/11-mediated phospholipase Cβ activity. In fact, B1R is constitutively active, whereas B2R exhibits little if any constitutive activity. To evaluate the role of the C-terminal domain in receptor G_q/11 coupling, we constructed chimeric and C-terminally truncated receptors. The slopes of the increase in basal and agonist-dependent cellular phosphoinositide hydrolysis as a function of receptor density in transiently transfected human embryonic kidney 293 cells provided parameters of receptor coupling. Exchanging the C-terminal domains between the two receptors revealed that these domains are largely responsible for the difference in coupling. B1R truncation showed that this receptor does not directly depend on the C-terminal domain for efficient coupling, although coupling is dramatically augmented by residues in the membrane-distal portion of the domain downstream from Tyr³²⁷. On the other hand, coupling of B2R is absolutely dependent on a membrane-proximal epitope in the C-terminal domain upstream from Lys³¹⁵. This epitope is adjacent to a basic residue, Arg³¹¹, which exerts an inhibitory effect on coupling. Arg³¹¹ is not conserved in B1R, and complementary mutations in B2R and B1R showed that this residue, together with previously identified serines and threonines, acts to attenuate the coupling efficacy of B2R. Therefore, the C-terminal domain participates intimately in the efficacy of B1R and B2R G_q/11 coupling by contributing both positive and negative regulatory epitopes." @default.
• W2113756625 created "2016-06-24" @default.
• W2113756625 creator A5008659861 @default.
• W2113756625 creator A5053233522 @default.
• W2113756625 date "2002-08-01" @default.
• W2113756625 modified "2023-10-16" @default.
• W2113756625 title "Negative and Positive Regulatory Epitopes in the C-Terminal Domains of the Human B1 and B2 Bradykinin Receptor Subtypes Determine Receptor Coupling Efficacy to G_9/11-Mediated Phospholipase Cβ Activity" @default.
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• W2113756625 doi "https://doi.org/10.1124/mol.62.2.281" @default.
• W2113756625 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/12130679" @default.
• W2113756625 hasPublicationYear "2002" @default.
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