POLYPEPTIDES that define a protein family termed RGS (for regulators of G-protein signalling) are encoded by the SST2 gene of the yeast Saccharomyces cerevisiae, the EGL-10 gene of the nematode Caenorhabdatis elegans, and several related mammalian genes. Genetic studies in invertebrates and mammalian cell-transfection experiments indicate that RGS proteins negatively regulate signalling pathways involving seven transmem-brane receptors and heterotrimeric G proteins1–3. However, the biochemical mechanism by which RGS proteins control these pathways is unknown. Here we report the characterization of human RGS10, a member of this protein family. Co-immunopre-cipitation studies demonstrate that RGS10 associates specifically with the activated forms of two related G-protein subunits, Gαi3 and Gα z, but fails to interact with the structurally and functionally distinct Gα s subunit. In vitro assays with purified proteins indicate that RGS10 increases potently and selectively the GTP hydrolytic activity of several members of the Gα i family, including Gα i3, Gα z and Gα o. These results demonstrate that RGS proteins can attenuate signalling pathways involving heterotrimeric G proteins by serving as GTPase-activating proteins for specific types of Gα subunits.
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Hunt, T., Fields, T., Casey, P. et al. RGS10 is a selective activator of Gαi GTPase activity. Nature 383, 175–177 (1996). https://doi.org/10.1038/383175a0
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