title: Specific in vivo binding of activator of G protein signalling 1 to the Gbeta1 subunit.
abstract: Activator of G protein signalling 1 (AGS1) is a Ras-like protein that affects signalling through heterotrimeric G proteins. Previous in vitro studies suggest that AGS1 can bind to G(alpha)-GDP subunits and promote nucleotide exchange, leading to activation of intracellular signalling pathways. This model is consistent with in vivo evidence demonstrating that AGS1 activates both G(alpha)- and G(betagamma)-dependent pathways in the absence of ligand. However, it does not easily explain how AGS1 blocks G(betagamma)-dependent, but not G(alpha)-dependent, signalling following receptor activation. We have used yeast two hybrid analysis and co-immunoprecipitation studies in mammalian cells to demonstrate a direct interaction between AGS1 and the G(beta1) subunit of heterotrimeric G proteins. The interaction is specific for G(beta1) and involves the cationic region of AGS1 and the C-terminal region of G(beta1). Possible implications of this novel interaction for the activity of AGS1 are discussed.
authors.affiliation: Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Hiskens
authors.forename: Manu
authors.initials: M
authors.lastname: Vatish
authors.forename: Claire
authors.initials: C
authors.lastname: Hill
authors.forename: John
authors.initials: J
authors.lastname: Davey
authors.forename: Graham
authors.initials: G
authors.lastname: Ladds
mesh_terms: D001665:Binding Sites; D002460:Cell Line; D044387:GTP-Binding Protein beta Subunits / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013379:Substrate Specificity; D020798:Two-Hybrid System Techniques; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D044387:GTP-Binding Protein beta Subunits; C400132:RASD1 protein, human; D018631:ras Proteins