DIFFERENT ALPHA-1-ADRENERGIC RECEPTOR SEQUENCES REQUIRED FOR ACTIVATING DIFFERENT G-ALPHA SUBUNITS OF GQ CLASS OF G-PROTEINS

In order to understand the specific interactions between receptors and guanine nucleotide-binding regulatory protein (G proteins), we attemp ted to delineate the alpha 1B-adrenergic receptor sequences involved i n activation of the alpha subunits of the Gq class of G proteins. A nu mber of specific mutations were introduced into the third inner loop o f the receptor, and the mutants were tested for their abilities to act ivate different G alpha subunits of the Gq class. Our results indicate that the receptor sequences required for activating G alpha q/11, G a lpha 14, or G alpha 16 are different. The sequence extending from resi dues Lys(240) to His(252) is required for activation of G alpha q/11, but not for activation of G alpha 14 or G alpha 16. Two segments in th e 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 Asn(2 26), and the other is located at the C terminus of the loop starting f rom residue Ser(278). The fatter contains a BBXXB motif, which is appa rently critical for G alpha 14 coupling, but not for G alpha 16 or G a lpha q/11 conpling. Furthermore, the three amino acids stretch (Tyr(21 7) to Val(219)) included in the N-terminal segment is not only require d 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.