title: Co-expression of Gbeta5 enhances the function of two Ggamma subunit-like domain-containing regulators of G protein signaling proteins.
abstract: Regulators of G protein signaling (RGS) stimulate the GTPase activity of G protein Galpha subunits and probably play additional roles. Some RGS proteins contain a Ggamma subunit-like (GGL) domain, which mediates a specific interaction with Gbeta5. The role of such interactions in RGS function is unclear. RGS proteins can accelerate the kinetics of coupling of G protein-coupled receptors to G-protein-gated inwardly rectifying K(+) (GIRK) channels. Therefore, we coupled m2-muscarinic acetylcholine receptors to GIRK channels in Xenopus oocytes to evaluate the effect of Gbeta5 on RGS function. Co-expression of either RGS7 or RGS9 modestly accelerated GIRK channel kinetics. When Gbeta5 was co-expressed with either RGS7 or RGS9, the acceleration of GIRK channel kinetics was strongly increased over that produced by RGS7 or RGS9 alone. RGS function was not enhanced by co-expression of Gbeta1, and co-expression of Gbeta5 alone had no effect on GIRK channel kinetics. Gbeta5 did not modulate the function either of RGS4, an RGS protein that lacks a GGL domain, or of a functional RGS7 construct in which the GGL domain was omitted. Enhancement of RGS7 function by Gbeta5 was not a consequence of an increase in the amount of plasma membrane or cytosolic RGS7 protein.
authors.affiliation: Division of Biology, California Institute of Technology, Pasadena, California 91125, USA.
authors.forename: A
authors.initials: A
authors.lastname: Kovoor
authors.forename: C K
authors.initials: CK
authors.lastname: Chen
authors.forename: W
authors.initials: W
authors.lastname: He
authors.forename: T G
authors.initials: TG
authors.lastname: Wensel
authors.forename: M I
authors.initials: MI
authors.lastname: Simon
authors.forename: H A
authors.initials: HA
authors.lastname: Lester
mesh_terms: D000818:Animals; D044387:GTP-Binding Protein beta Subunits; D019204:GTP-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D020962:Heterotrimeric GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D015640:Ion Channel Gating; D015221:Potassium Channels / Q000378:metabolism; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D014981:Xenopus
chemical_list: D044387:GTP-Binding Protein beta Subunits; C094668:Gnb5 protein, mouse; D015221:Potassium Channels; D019204:GTP-Binding Proteins; D020962:Heterotrimeric GTP-Binding Proteins