RGS family members: GTPase-activating proteins for heterotrimeric G-protein alpha-subunits

Nature. 1996 Sep 12;383(6596):172-5. doi: 10.1038/383172a0.


Signaling pathways using heterotrimeric guanine-nucleotide-binding-proteins (G proteins) trigger physiological responses elicited by hormones, neurotransmitters and sensory stimuli. GTP binding activates G proteins by dissociating G alpha from G beta gamma subunits, and GTP hydrolysis by G alpha subunits deactivates G proteins by allowing heterotrimers to reform. However, deactivation of G-protein signalling pathways in vivo can occur 10- to 100-fold faster than the rate of GTP hydrolysis of G alpha subunits in vitro, suggesting that GTPase-activating proteins (GAPs) deactivate G alpha subunits. Here we report that RGS (for regulator of G-protein signalling) proteins are GAPs for G alpha subunits. RGS1, RGS4 and GAIP (for G alpha-interacting protein) bind specifically and tightly to G alphai and G alpha0 in cell membranes treated with GDP and AlF4(-), and are GAPs for G alphai, G alpha0 and transducin alpha-subunits, but not for G alphas. Thus, these RGS proteins are likely to regulate a subset of the G-protein signalling pathways in mammalian cells. Our results provide insight into the mechanisms that govern the duration and specificity of physiological responses elicited by G-protein-mediated signalling pathways.

Publication types

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

MeSH terms

  • Animals
  • Catalysis
  • Cattle
  • Cell Membrane / metabolism
  • Enzyme Activation
  • GTP Phosphohydrolases / metabolism*
  • GTP-Binding Proteins / metabolism*
  • GTPase-Activating Proteins
  • Guanosine Diphosphate / metabolism
  • Guanosine Triphosphate / metabolism
  • In Vitro Techniques
  • Phosphoproteins / metabolism
  • Proteins / metabolism*
  • RGS Proteins*
  • Signal Transduction


  • GTPase-Activating Proteins
  • Phosphoproteins
  • Proteins
  • RGS Proteins
  • regulator of G-protein signalling 19
  • Guanosine Diphosphate
  • RGS4 protein
  • Guanosine Triphosphate
  • GTP Phosphohydrolases
  • GTP-Binding Proteins