Abstract
In order to understand the specific interactions between receptors and guanine nucleotide-binding regulatory protein (G proteins), we attempted to delineate the alpha 1 B-adrenergic receptor sequences involved in activation of the alpha subunits of the Gq class of G proteins. A number of specific mutations were introduced into the third inner loop of the receptor, and the mutants were tested for their abilities to activate different G alpha subunits of the Gq class. Our results indicate that the receptor sequences required for activating G alpha q/11, G alpha 14, or G alpha 16 are different. The sequence extending from residues Lys240 to His252 is required for activation of G alpha q/11, but not for activation of G alpha 14 or G alpha 16. Two segments in the third loop of the receptor are required for activation of G alpha 14: one is located at the N terminus of the loop ending at residue Asn226, and the other is located at the C terminus of the loop starting from residue Ser278. The latter contains a BBXXB motif, which is apparently critical for G alpha 14 coupling, but not for G alpha 16 or G alpha q/11 coupling. Furthermore, the three amino acids stretch (Tyr217 to Val219) included in the N-terminal segment is not only required for G alpha 14 coupling, but also for G alpha q/11 coupling. It may be involved to some extent in G alpha 16 coupling as well.
Highlights
From the Department of Pharmacology, University of Rochester, Rochester, New York 14642 and the §Division of Biology, California Institute of Technology, Pasadena, California 91125
We have previously demonstrated that the alB-adrenergic receptor can couple to all the Ga subunits of the Gq class of G
In order to determine whether the alB-adrenergic receptor sequences involved in activating Ga14 and Ga16 are the same as the ones required for activating Gaq/ll [22], we made a specific mutation in the alB-adrenergic receptor by deleting amino acids from residues Lys240 to His25 2 (Fig. 1)
Summary
Vol 270, No 17, Issue of April 28, pp. 9828-9832, 1995 Printed in U.S.A. Different aI-Adrenergic Receptor Sequences Required for Activating Different G« Subunits of Gq Class of G Proteins*. 2) The use of antisense oligonucleotides to inhibit expression of various subunits of G proteins This approach has been successfully applied to reveal the specific interactions among the receptors, Ga, G/3, and G')' in GH3 cells [8, 9]. 4) The use of the cotransfection system, in which cells are transfected with cDNAs encoding receptors and G proteins with subsequent measurement of ligand-induced responses This approach has been used to study coupling of the IL-8 [13], C5a [14] and a-adrenergic [15,16,17,18] receptors to the a subunits of the Gq and Gi classes. Our results indicate that different alB-adrenergic receptor sequences are involved in coupling to Goq/Ll , Ga14, or Ga16
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