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

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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Watson, N., Linder, M., Druey, K. et al. RGS family members: GTPase-activating proteins for heterotrimeric G-protein α-subunits. Nature 383, 172–175 (1996). https://doi.org/10.1038/383172a0

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