PT - JOURNAL ARTICLE AU - Sejal M. Mody AU - Maurice K. C. Ho AU - Sushma A. Joshi AU - Yung H. Wong TI - Incorporation of Gα<sub>z</sub>-Specific Sequence at the Carboxyl Terminus Increases the Promiscuity of Gα<sub>16</sub>toward G<sub>i</sub>-Coupled Receptors DP - 2000 Jan 01 TA - Molecular Pharmacology PG - 13--23 VI - 57 IP - 1 4099 - http://molpharm.aspetjournals.org/content/57/1/13.short 4100 - http://molpharm.aspetjournals.org/content/57/1/13.full SO - Mol Pharmacol2000 Jan 01; 57 AB - Although the promiscuous nature of G16 allows it to interact with numerous G protein-coupled receptors, several Gi-linked receptors are incapable of activating phospholipase C via G16. A series of chimeras between Gα16 and Gαz were constructed and assayed for their ability to mediate receptor-induced stimulation of phospholipase C. Two Gα16/z chimeras harboring 25 or 44 Gαz-specific sequences at their C termini (named 16z25 and 16z44) were capable of responding to 14 different Gi-coupled receptors tested, including those that were either unable to associate with Gα16 (melatonin Mel1c) or activate Gα16 weakly (μ-opioid and type 1 somatostatin). Agonist-induced stimulation of phospholipase C was more efficiently mediated (higher maximal and lower EC50 value) by 16z44 than by Gα16. Both 16z25 and 16z44 were also coupled to Gs- and Gq-linked receptors. Incorporation of Gαz sequence at the N terminus of Gα16 did not further enhance the ability of the chimeras to interact with Gi-coupled receptors. Expression of the various chimeras was verified by immunodetection and functional analysis of their constitutively activated mutants. These results show that the incorporation of α4/β6 and α5 regions of Gαz into a Gα16 backbone can improve the recognition of Gi-coupled receptors. Gα16/zchimeras with expanded capability to interact with Gi-linked receptors may be used to link orphan receptors to the stimulation of phospholipase C. The American Society for Pharmacology and Experimental Therapeutics