RGS10 is a selective activator of G alpha i GTPase activity.
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 transmembrane receptors and heterotrimeric G proteins. 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-immunoprecipitation studies demonstrate that RGS10 associates specifically with the activated forms of two related G-protein subunits, G alphai3, and G alphaz, but fails to interact with the structurally and functionally distinct G alphas subunit. In vitro assays with purified proteins indicate that RGS10 increases potently and selectively the GTP hydrolytic activity of several members of the G alphai family, including G alphai3, G alphaz, and G alpha0. These results demonstrate that RGS proteins can attenuate signalling pathways involving heterotrimeric G proteins by serving as GTPase-activating proteins for specific types of G alpha subunits.
Hunt
T W
TW
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Fields
T A
TA
Casey
P J
PJ
Peralta
E G
EG
D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D004789:Enzyme Activation; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D006868:Hydrolysis; D008969:Molecular Sequence Data; D011233:Precipitin Tests; D011506:Proteins / Q000378:metabolism*; D020710:RGS Proteins; D051381:Rats; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
D011506:Proteins; D020710:RGS Proteins; C101113:RGS10 protein, human; C491067:Rgs10 protein, rat; D006160:Guanosine Triphosphate; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins