Properties of Arg389-beta1-adrenoceptor-Gsalpha fusion proteins: comparison with Gly389-beta1-adrenoceptor-Gsalpha fusion proteins.
The human beta1-adrenoceptor (beta1AR) exists in several isoforms and activates adenylyl cyclase (AC) via Gs-proteins. The Arg389-isoform of the beta1AR (beta1AR-R389) expressed in CHW cells is much more efficient than the Gly389 isoform of the beta1AR (beta1AR-G389) at stabilizing the ternary complex and activating AC (Mason et al. 1999). The beta1AR-G389 fused to the Gsalpha splice variants GsalphaL or GsalphaS is efficient at stabilizing the ternary complex and activating AC (Wenzel-Seifert et al. 2002). Here, we show that beta1AR-R389-Gsalpha fusion proteins and beta1AR-G389-Gsalpha fusion proteins are similarly efficient at stabilizing the ternary complex and activating AC. In terms of agonist efficacies and agonist potencies in the [35S]guanosine 5'-O-(3-thiotriphosphate) binding assay, beta1AR-R389-Gsalpha fusion proteins and beta1AR-G389-Gsalpha fusion proteins are similar, too. Our present data fit to an increasing number of clinical studies that failed to detect physiology- or pathology-related functional differences between beta1AR-R389 and beta1AR-G389.
Wenzel-Seifert
Katharina
K
Department of Pharmacology and Toxicology, The University of Kansas, Lawrence, Kansas 66045-7582, USA.
Seifert
Roland
R
D000262:Adenylyl Cyclases / Q000378:metabolism; D019943:Amino Acid Substitution; D003001:Cloning, Molecular; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D015151:Immunoblotting; D008024:Ligands; D008565:Membrane Proteins / Q000378:metabolism; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000819:agonists / Q000235:genetics / Q000378:metabolism*
D008024:Ligands; D008565:Membrane Proteins; D018342:Receptors, Adrenergic, beta-1; D011993:Recombinant Fusion Proteins; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate; D019205:GTP-Binding Protein alpha Subunits, Gs; D000262:Adenylyl Cyclases