RGS10 is a selective activator of G alpha i GTPase activity

Nature. 1996 Sep 12;383(6596):175-7. doi: 10.1038/383175a0.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cloning, Molecular
  • Enzyme Activation
  • GTP Phosphohydrolases / metabolism*
  • GTP-Binding Proteins / metabolism*
  • Guanosine Triphosphate / metabolism
  • HeLa Cells
  • Humans
  • Hydrolysis
  • Molecular Sequence Data
  • Precipitin Tests
  • Proteins / metabolism*
  • RGS Proteins*
  • Rats
  • Sequence Homology, Amino Acid
  • Signal Transduction

Substances

  • Proteins
  • RGS Proteins
  • RGS10 protein, human
  • Rgs10 protein, rat
  • Guanosine Triphosphate
  • GTP Phosphohydrolases
  • GTP-Binding Proteins

Associated data

  • GENBANK/H87415