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Molecular Pharmacology

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Abstract

Involvement of specific hydrophobic, but not hydrophilic, amino acids in the third intracellular loop of the beta-adrenergic receptor in the activation of Gs.

A H Cheung, R R Huang and C D Strader
Molecular Pharmacology June 1992, 41 (6) 1061-1065;
A H Cheung
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R R Huang
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C D Strader
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Abstract

Mutagenesis and biochemical analysis have indicated that amino acid residues at the amino terminus of the third intracellular loops of guanine nucleotide-binding protein (G protein)-coupled receptors are important in mediating the coupling of the receptors to G proteins. Because the primary sequence of this region is not conserved among all receptors that couple to the same G protein, it has been suggested that some other physicochemical property of this domain may determine G protein activation. To determine the relative contributions of charge distribution and amino acid side chain interactions within this domain of the beta-adrenergic receptor (beta AR) to the activation of the G protein Gs, point mutations were introduced into this region of the beta AR. Replacement of all four of the basic amino acid residues within this region (amino acids 222-236) with serine residues had a negligible effect on the ability of the beta AR to activate Gs. In contrast, replacement of the hydrophobic amino acids within this same region with leucine residues resulted in a mutant receptor that was poorly coupled to Gs. These results suggest that specific hydrophobic interactions within this region of the receptor may play a more significant role than ionic or hydrophilic interactions in mediating G protein activation.

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Molecular Pharmacology
Vol. 41, Issue 6
1 Jun 1992
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Abstract

Involvement of specific hydrophobic, but not hydrophilic, amino acids in the third intracellular loop of the beta-adrenergic receptor in the activation of Gs.

A H Cheung, R R Huang and C D Strader
Molecular Pharmacology June 1, 1992, 41 (6) 1061-1065;

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Abstract

Involvement of specific hydrophobic, but not hydrophilic, amino acids in the third intracellular loop of the beta-adrenergic receptor in the activation of Gs.

A H Cheung, R R Huang and C D Strader
Molecular Pharmacology June 1, 1992, 41 (6) 1061-1065;
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