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Sci. STKE, 7 January 2003
Vol. 2003, Issue 164, p. tw6
[DOI: 10.1126/scisignal.1642003tw6]

EDITORS' CHOICE

G Proteins New G Protein Interactions

Two groups have uncovered new wrinkles in reactions involving heterotrimeric guanosine triphosphate (GTP)-binding proteins (G proteins). Ligand binding to G protein-coupled receptors (GPCRs) activates G proteins by catalyzing guanine nucleotide exchange and dissociation of the GTP-bound α subunit (Gα) from the β{gamma} heterodimer (Gβ{gamma}). Both subunits are then free to activate various effectors. Ribas et al. partially purified a ligand-independent G-protein activator, NG108-15 G-protein activator (NG-GPA), from the neuroblastoma-glioma hybrid NG108-15. NG-GPA stimulated guanosine 5'-O-thiotriphosphate (GTP{gamma}S) binding to purified brain G protein, as well as to recombinant Gαo and Gαi, and inhibited adenylyl cyclase activity in DDT1-MF-2 cell membranes. NG-GPA's stimulation of GTP{gamma}S binding, unlike GPCR-stimulated GTP{gamma}S binding, was unaffected by treatment with pertussis toxin, which prevents agonist-induced receptor interactions with the Gi family of G proteins, suggesting that NG-GPA interacts with the G protein through a previously unidentified regulatory domain. Dell et al. used a yeast two-hybrid screen to identify new Gβ{gamma} effectors and isolated three proteins containing WD40 motifs (which Gβ{gamma} also contains) that bound to Gβ{gamma}. Gβ{gamma} interaction with two of these proteins, receptor for activated C kinase 1 (RACK1) and dynein intermediate chain (DIC), was confirmed by Western analysis of immunoprecipitates. A RACK1 fusion protein bound to both Gβ1{gamma}1 and the heterotrimeric Gαtβ1{gamma}1 transducin heterotrimer but not to Gαt alone; Gαtβ1{gamma}1 had a higher binding affinity than Gβ1{gamma}1. RACK1 interaction with Gαtβ1{gamma}1 was surprising, because few proteins other than GPCRs interact with the heterotrimer. Indeed, all known Gβ{gamma} effectors bind to the Gα-interacting region, suggesting a novel mechanism for RACK1-G protein interaction.

C. Ribas, A. Takesono, M. Sato, J. D. Hildebrandt, S. M. Lanier, Pertussis toxin-insensitive activation of the heterotrimeric G-proteins Gi/Go by the NG108-15 G-protein activator. J. Biol. Chem. 277, 50223-50225 (2002). [Abstract] [Full Text]

E. J. Dell, J. Connor, S. Chen, E. G. Stebbins, N. P. Skiba, D. Mochly-Rosen, H. E. Hamm, The β{gamma} subunit of heterotrimeric G proteins interacts with RACK1 and two other WD repeat proteins. J. Biol. Chem. 277, 49888-49895 (2002). [Abstract] [Full Text]

Citation: New G Protein Interactions. Sci. STKE 2003, tw6 (2003).

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