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

Nature volume 383, pages 172175 (12 September 1996) | Download Citation

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Abstract

SIGNALLING pathways using heterotrimeric guanine-nucleotide-binding-proteins (G proteins) trigger physiological responses elicited by hormones, neurotransmitters and sensory stimuli1,2. GTP binding activates G proteins by dissociating Gα from Gβγ subunits, and GTP hydrolysis by Gα 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 Gα subunits in vitro3–8, suggesting that GTPase-activating proteins (GAPs) deactivate Gα subunits. Here we report that RGS9,10 (for regulator of G-protein signalling) proteins are GAPs for Gα subunits. RGS1, RGS4 and GAIP (for Gα-interacting protein17) bind specifically and tightly to GαI and Gαo in cell membranes treated with GDP and AlF4, and are GAPs for GαIo and transducin α-subunits, but not for Gαs. 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.

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Affiliations

  1. Department of Cell Biology and Physiology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, Missouri 63110, USA

    • Ned Watson
    • , Maurine E. Linder
    •  & Kendall J. Blumer
  2. Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA

    • Kirk M. Druey
    •  & John H. Kehrl

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https://doi.org/10.1038/383172a0

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