RGS family members: GTPase-activating proteins for heterotrimeric G-protein alpha-subunits.
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.
Watson
N
N
Department of Cell Biology and Physiology, Washington University School of Medicine, St Louis, Missouri 63110, USA.
Linder
M E
ME
Druey
K M
KM
Kehrl
J H
JH
Blumer
K J
KJ
D000818:Animals; D002384:Catalysis; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D004789:Enzyme Activation; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D020690:GTPase-Activating Proteins; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D066298:In Vitro Techniques; D010750:Phosphoproteins / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D020710:RGS Proteins; D015398:Signal Transduction
D020690:GTPase-Activating Proteins; D010750:Phosphoproteins; D011506:Proteins; D020710:RGS Proteins; C097187:regulator of G-protein signalling 19; D006153:Guanosine Diphosphate; C098799:RGS4 protein; D006160:Guanosine Triphosphate; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins