Interaction of Gβ3s, a splice variant of the G-protein Gβ3, with Gγ- and Gα-proteins

摘要: Abstract The T-allele of a polymorphism (C825T) in the gene G-protein β3-subunit is associated with complex phenotype (hypertension, obesity, altered drug responses) and occurrence splice variant termed Gβ3s which lacks one seven WD-domains that compose Gβ-proteins. Here, we analysed Gβγ dimer formation Gα activation by Gβ3s, key functional characteristics Cleavage protection assays frequently used to analyse Gβ1γ Gβ2γ failed for Gβ3 while coprecipitation assays, dimerization Gγ5, Gγ8 c Gγ12 could be demonstrated. Upon expression COS-7 Sf9 insect cells, binding GTPγS Gα-proteins induced mastoparan-7 M 2 muscarinic acetylcholine receptor was facilitated comparison cells overexpressing wildtype Gβ3, as indicated twofold reduced agonist EC 50 values. Together, these results indicate biologically active Gβ-protein may mediate enhanced signal transduction observed 825T-allele.