title: Dominant negative effects of a Gbeta mutant on G-protein coupled inward rectifier K+ channel.
abstract: HEK293 cells were transfected with cDNAs for Gbeta1(W332A) [a mutant Gbeta1], Ggamma2, and inward rectifier K+ channels (Kir3.1/Kir3.2). Application of Gbeta1gamma2 protein to these cells activated the K+ channels only slightly. When mu-opioid receptors and Kir3.1/Kir3.2 were transfected, application of a mu-opioid agonist induced a Kir3 current. However, co-expression of Gbeta1(W332A) suppressed this current. Most likely, Gbeta1(W332A) inhibited the action of the endogenous Gbeta. Such a dominant negative effect of Gbeta1(W332A) was also observed in neuronal Kir3 channels in locus coeruleus. The mutant, Gbeta1(W332A) protein, although inactive, retains its ability to bind Kir3 and prevents the wild type Gbeta from activating the channel.
authors.affiliation: Department of Pharmacology, College of Medicine, University of Illinois at Chicago, 835 S. Wolcott Av., Chicago, IL 60612-7343, USA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhao
authors.forename: Abla M
authors.initials: AM
authors.lastname: Albsoul-Younes
authors.forename: Peng
authors.initials: P
authors.lastname: Zhao
authors.forename: Tohru
authors.initials: T
authors.lastname: Kozasa
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Nakajima
authors.forename: Shigehiro
authors.initials: S
authors.lastname: Nakajima
mesh_terms: D000818:Animals; D002417:Cattle; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000378:metabolism*; D044387:GTP-Binding Protein beta Subunits / Q000235:genetics* / Q000378:metabolism*; D044388:GTP-Binding Protein gamma Subunits / Q000378:metabolism; D005799:Genes, Dominant / Q000235:genetics*; D006801:Humans; D008125:Locus Coeruleus / Q000502:physiology; D051379:Mice; D009154:Mutation / Q000235:genetics*; D051381:Rats; D020318:Rats, Long-Evans; D017450:Receptors, Opioid, mu / Q000378:metabolism; D013997:Time Factors
chemical_list: D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D017450:Receptors, Opioid, mu