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.
Wu
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D
Department of Pharmacology, University of Rochester Medical Center, New York 14642, USA.
Kuang
Y
Y
Wu
Y
Y
Jiang
H
H
D000818:Animals; D002478:Cells, Cultured; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D010738:Type C Phospholipases / Q000378:metabolism
D018343:Receptors, Adrenergic, beta-2; D011994:Recombinant Proteins; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D009638:Norepinephrine