An Asp79Asn mutation of the alpha2A-adrenoceptor interferes equally with agonist activation of individual Gialpha-family G protein subtypes.
The quantitative effects of an Asp79Asn mutation in the porcine alpha2A-adrenoceptor on adrenaline-mediated stimulation of the alpha subunit of individual members of the Gi family of G proteins were assessed by measuring GTP turnover number for fusion proteins between the wild type or mutated receptor and pertussis toxin-resistant forms of each of Gi1, Gi2 and Gi3. In each case the receptor mutation limited activation of the G protein to 8-14% of that produced by the wild type receptor. Previous demonstration that in a single cell this mutation selectively interferes with alpha2A-adrenoceptor regulation of distinct effector end points transduced by Gi family members must therefore reflect differential requirements for amplification or the cellular location of individual, co-expressed, G proteins.
Ward
R J
RJ
Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, University of Glasgow, UK.
Milligan
G
G
D019943:Amino Acid Substitution; D000818:Animals; D001216:Asparagine / Q000235:genetics; D001224:Aspartic Acid / Q000235:genetics; D019556:COS Cells; D002462:Cell Membrane / Q000378:metabolism; D004837:Epinephrine / Q000494:pharmacology; D020558:GTP Phosphohydrolases / Q000378:metabolism; D051960:GTP-Binding Protein alpha Subunit, Gi2; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism*; D007700:Kinetics; D009154:Mutation; D017354:Point Mutation; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics* / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013552:Swine
D011518:Proto-Oncogene Proteins; D018341:Receptors, Adrenergic, alpha-2; D011993:Recombinant Fusion Proteins; D001224:Aspartic Acid; D001216:Asparagine; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D051960:GTP-Binding Protein alpha Subunit, Gi2; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D020962:Heterotrimeric GTP-Binding Proteins; D004837:Epinephrine