Selective coupling of β2-adrenergic receptor to hematopoietic-specific G proteins

Abstract

The coupling of the β2-adrenergic receptor (AR) to the α subunits of the Gq class of G proteins was investigated in a cotransfection system. COS- 7 cells cotransfected with the β2-AR cDNA and the Gα15 or Gα16 cDNA showed marked norepinephrine-induced increases in accumulation of inositol phosphates in a concentration-dependent manner. However, cells cotransfected with the cDNA encoding Gαq, Gα11, or Gα14 instead of Gα16 gave no ligand-dependent activation of phospholipase C (PLC). The facts that the β- AR agonist isoprenaline can also induce activation of PLC in cells coexpressing β2-AR and Gα16 and that the β2-AR-specific antagonist propranolol can block norepinephrine-induced activation of PLC in these cotransfected cells further indicate that it is the β2-AR that mediates the activation of phospholipase C in these cotransfected cells. To test the possibility of involvement of Gβγ, a Gβγ antagonist, Gγ3 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 Gβγ- mediated but not Gα-mediated activation of PLC. The result that the Gγ3 mutant could not inhibit β2-adrenergic receptor-mediated activation of PLC in cells cotransfected with the Gα16 cDNA suggests that Gβγ is unlikely to be a major mediator of β2-adrenergic receptor-induced activation of PLC. Thus, we conclude that the β2-adrenergic receptor can specifically couple to Gα15 and Gα16, but not to Gαq, Gα11, or Gα14 to activate PLC.