Gα14 links a variety of Gi- and Gs-coupled receptors to the stimulation of phospholipase C

1 The bovine G alpha (14) is a member of the G(q) subfamily of G proteins that can regulate phospholipase C beta isoforms but the extent to which G alpha (14) recognizes different receptor classes is not known. 2 G alpha (14) was cotransfected with a variety of receptors in COS-7 cells, and agonist-induced stimulation of phospholipase C was then measured. 3 Activation of the type 2 but not type 1 somatostatin receptor in cells coexpressing G alpha (14) stimulated the accumulation of inositol phosphates; functional expression of both subtypes of somatostatin receptors was determined by the ability of somatostatin to inhibit cyclic AMP accumulation. 4 Among the three opioid receptors (mu, delta, and kappa), only the delta receptor was capable of stimulating IP formation when coexpressed with G alpha (14) in COS-7 cells. 5 A panel of G(i)- and G(s)-linked receptors was screened for their ability to stimulate IP accumulation via G alpha (14). The adenosine A(1), complement C5a, dopamine D-1, D-2 and D-5, formyl peptide, luteinizing hormone, secretin, and the three subtypes of melatonin (mt1, MT2, and Xenopus) receptors were all incapable of activating G alpha (14), while the alpha (2)- and Pz-adrenoceptors were able to do so. 6 G alpha (14)-mediated stimulation of phospholipase C beta was agonist dose-dependent. These data demonstrate that although G alpha (14) can interact with different classes of receptors, it is much less promiscuous than G alpha (15) or G alpha (16).