title: Role of the G protein gamma subunit in beta gamma complex modulation of phospholipase Cbeta function.
abstract: The G protein betagamma complex regulates a wide range of effectors, including the phospholipase C isozymes (PLCbetas). Different domains on the beta subunit are known to contact phospholipase Cbeta and affect its regulation. In contrast, the role of the gamma subunit in Gbetagamma modulation of PLCbeta function is not known. Results here show that the gamma subunit C-terminal domain is involved in mediating Gbetagamma interactions with phospholipase Cbeta. Mutations were introduced to alter the position of the post-translational prenyl modification at the C terminus of the gamma subunit with reference to the beta subunit. These mutants were appropriately post-translationally modified with the geranylgeranyl moiety. A deletion that shortened the C-terminal domain, insertions that extended this domain, and a point mutation, F59A, that disrupted the interaction of this domain with the beta subunit were all affected in their ability to activate PLCbeta to varying degrees. All mutants, however, interacted equally effectively with the G(o)alpha subunit. The results indicate that the G protein gamma subunit plays a direct role in the modulation of effector function by the betagamma complex.
authors.affiliation: Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: Muslum
authors.initials: M
authors.lastname: Akgoz
authors.forename: Inaki
authors.initials: I
authors.lastname: Azpiazu
authors.forename: Vani
authors.initials: V
authors.lastname: Kalyanaraman
authors.forename: N
authors.initials: N
authors.lastname: Gautam
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D019281:Dimerization; D004305:Dose-Response Relationship, Drug; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D017353:Gene Deletion; D020962:Heterotrimeric GTP-Binding Proteins / Q000737:chemistry* / Q000502:physiology*; D007313:Insecta; D007527:Isoenzymes / Q000737:chemistry* / Q000502:physiology*; D013058:Mass Spectrometry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D054799:Phospholipase C beta; D017354:Point Mutation; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000378:metabolism; D013997:Time Factors; D014357:Trypsin / Q000494:pharmacology; D010738:Type C Phospholipases / Q000737:chemistry* / Q000502:physiology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: C118981:G-protein Beta gamma; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D007527:Isoenzymes; D011994:Recombinant Proteins; D010566:Virulence Factors, Bordetella; D000244:Adenosine Diphosphate; D010738:Type C Phospholipases; D054799:Phospholipase C beta; D014357:Trypsin; D020962:Heterotrimeric GTP-Binding Proteins