alexa Identification of a domain in the angiotensin II type 1 receptor determining Gq coupling by the use of receptor chimeras.
Cardiology

Cardiology

Journal of Hypertension: Open Access

Author(s): Wang C, Jayadev S, Escobedo JA

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Abstract The angiotensin II type 1 (AT1R) and type 2 (AT2R) receptors belong to the seven transmembrane receptor superfamily. Previous studies have suggested that the AT1R couples to a Gq signaling pathway, whereas the AT2R does not associate with Gq. To identify the role that individual intracellular domains play in AT1R function, AT1R/AT2R chimeric receptors were prepared by substitution of intracellular loops. CHO cells expressing these chimeras were used to test angiotensin II-induced c-fos expression and Ca2+ mobilization which are involved in the AT1R signaling pathway through Gq coupling. Substitution of the second intracellular loop (IC2) and the cytoplasmic tail between the two receptors did not affect AT1R function. However, exchange of the third intracellular loop (IC3) resulted in the loss of function in the AT1R and conferred to the AT2R the ability to constitutively activate the fos promoter. These findings suggest that the third intracellular loop of the AT1R is critical for Gq coupling. Substitution of discrete amino acid sequences of the third intracellular loop indicate that its N-terminal and C-terminal portions, especially the seven amino acids 219-225 in the N-terminal portion, are important for AT1R function, and that the intermediate portion of this loop is not required for Gq coupling.
This article was published in J Biol Chem and referenced in Journal of Hypertension: Open Access

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