Hundreds or thousands of chemical and physical stimuli regulate the functions of eukaryotic cells by controlling the activities of a surprisingly small number of core signaling units that have been duplicated and adapted to achieve the necessary diversity. The most prevalent of these units, at least in animal cells, are three-protein modules consisting of signal recognition elements (receptors)...

GTPase-activating proteins (GAPs) regulate heterotrimeric G proteins by increasing the rates at which their subunits hydrolyze bound GTP and thus return to the inactive state. G protein GAPs act allosterically on G subunits, in contrast to GAPs for the Ras-like monomeric GTP-binding proteins. Although they do not contribute directly to the chemistry of GTP hydrolysis, G protein GAPs can acceler...

Slow synaptic potentials are generated when metabotropic G-protein-coupled receptors activate heterotrimeric G-proteins, which in turn modulate ion channels. Many neurons generate excitatory postsynaptic potentials mediated by G-proteins of the G q/11 family, which in turn activate phospholipase C. Accessory GTPase-activating proteins (GAPs) are thought to be required to accelerate GTP hydrolys...

Regulators of G protein signaling (RGS) proteins accelerate the GTPase activity of Galpha protein subunits in vitro, negatively regulating G protein-coupled receptor signaling. The physiological role of mammalian RGS proteins is largely unknown. The RGS family member rgs2 was cloned as an immediate early response gene up-regulated in T lymphocytes after activation. To investigate the role of RG...

RGS2 and RGS4 were studied for their effects as GTPase activating proteins (GAPs) on receptor-activated G(i) in a novel steady-state assay using membranes from Sf9 cells quadruply infected with baculoviruses encoding the m2 muscarinic receptor, G(alphai2), G(beta1), and G(gamma2). In the presence of the muscarinic agonist carbachol, regulator of G protein signaling 2 (RGS2) and RGS4 each produc...

Two Chimeric Regulator of G-protein Signaling (RGS) Proteins Differentially Modulate Soybean Heterotrimeric G-protein Cycle* Swarup Roy Choudhury, Corey S. Westfall, John P. Laborde, Naveen C. Bisht, Joseph M. Jez, Sona Pandey From the Donald Danforth Plant Science Center, 975 North Warson Road, St. Louis, MO, 63132, USA; Department of Biology, Washington University, One Brookings Drive, Campus...

Heterotrimeric GTP-binding proteins (G proteins) are intracellular signaling molecules that are activated by seven transmembrane receptors (Gilman, 1987; Hamm and Gilchrist, 1996; Neer, 1995). Heterotrimeric G proteins are composed of α, β and γ subunits and there are multiple types of each subunit. Seven transmembrane receptors for hormones, cytokines and other agonists have guanine nucleotide...

Signaling of G protein-coupled receptors (GPCRs) is regulated by different mechanisms. One of these involves regulators of G protein signaling (RGS), which are diverse and multifunctional proteins that bind to active Galpha subunits of G proteins and act as GTPase-activating proteins. Little is known about the molecular mechanisms that govern the selective use of RGS proteins in living cells. W...

RGS proteins act as negative regulators of G protein signaling, and there is growing evidence that the RGS family is important for regulating signaling in neurons. Two articles in this issue of Neuron (Martemyanov et al. and Rahman et al.) shed light on the function of one family member, RGS9-2, in behavioral responses to dopamine signaling in the striatum and on the relationship between its st...

Axin, a negative regulator of the Wnt signaling pathway, contains a canonical regulator of G protein signaling (RGS) core domain. Herein, we demonstrate both in vitro and in cells that this domain interacts with the subunit of the heterotrimeric G protein G12 but not with the closely related G 13 or with several other heterotrimeric G proteins. Axin preferentially binds the activated form of G ...