RGS family members: GTPase-activating proteins for heterotrimeric G-protein alpha-subunits.
Watson, Ned; Linder, Maurine E.; Druey, Kirk M.; Kehrl, John H.; Blumer, Kendall J.
[Letter] Nature. 383(6596):172-175, September 12, 1996.

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Signalling pathways using heterotrimeric guanine-nucleotide-binding-proteins (G proteins) trigger physiological responses elicited by hormones, neurotransmitters and sensory stimuli [1,2]. 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 [3-8], suggesting that GTPase-activating proteins (GAPs) deactivate G alpha subunits. Here we report that RGS [9,10] (for regulator of G-protein signalling) proteins are GAPs for G alpha subunits. RGS1, RGS4 and GAIP (for G alpha-interacting protein [17]) bind specifically and tightly to G alphai and G alpha sub o in cell membranes treated with GDP and A1F4 sup -, and are GAPs for G alphai, G alphao 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.

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