Selective coupling of beta 2-adrenergic receptor to hematopoietic-specific G proteins

The coupling of the beta 2-adrenergic receptor (AR) to the alpha subunits of the Gq class of G proteins was investigated in a cotransfection system. COS-7 cells cotransfected with the beta 2-AR cDNA and the G alpha 15 or G alpha 16 cDNA showed marked norepinephrine-induced increases in accumulation of inositol phosphates in a concentration-dependent manner. However, cells cotransfected with the cDNA encoding G alpha q, G alpha 11, or G alpha 14 instead of G alpha 16 gave no ligand-dependent activation of phospholipase C (PLC). The facts that the beta-AR agonist isoprenaline can also induce activation of PLC in cells coexpressing beta 2-AR and G alpha 16 and that the beta 2-AR-specific antagonist propranolol can block norepinephrine-induced activation of PLC in these cotransfected cells further indicate that it is the beta 2-AR that mediates the activation of phospholipase C in these cotransfected cells. To test the possibility of involvement of G beta gamma, a G beta gamma antagonist, G gamma 3 mutant with substitution of a Ser residue for the C-terminal Cys residue, was used because this protein, when expressed in COS-7 cells, can inhibit only G beta gamma-mediated but not G alpha-mediated activation of PLC. The result that the G gamma 3 mutant could not inhibit beta 2-adrenergic receptor-mediated activation of PLC in cells cotransfected with the G alpha 16 cDNA suggests that G beta gamma is unlikely to be a major mediator of beta 2-adrenergic receptor-induced activation of PLC. Thus, we conclude that the beta 2-adrenergic receptor can specifically couple to G alpha 15 and G alpha 16, but not to G alpha q, G alpha 11, or G alpha 14 to activate PLC.