Fine-Tuning of GPCR Signals by Intracellular G Protein Modulators

Bourne, 1991, The GTPase superfamily: conserved structure and molecular mechanism, Nature, 349, 117, 10.1038/349117a0 Wittinghofer, 2011, Structure-function relationships of the G domain, a canonical switch motif, Annu Rev Biochem, 80, 943, 10.1146/annurev-biochem-062708-134043 Higashijima, 1987, Effects of Mg2+ and the beta gamma-subunit complex on the interactions of guanine nucleotides with G proteins, J Biol Chem, 262, 762, 10.1016/S0021-9258(19)75851-7 Clapham, 1997, G protein beta gamma subunits, Annu Rev Pharmacol Toxicol, 37, 167, 10.1146/annurev.pharmtox.37.1.167 Chidiac, 1999, Phospholipase C-beta1 directly accelerates GTP hydrolysis by Galphaq and acceleration is inhibited by Gbeta gamma subunits, J Biol Chem, 274, 19639, 10.1074/jbc.274.28.19639 Suzuki, 2009, Regulation and physiological functions of G12/13-mediated signaling pathways, Neurosignals, 17, 55, 10.1159/000186690 Abramow-Newerly, 2006, RGS proteins have a signaling complex: interactions between RGS proteins and GPCRs, effectors, and auxiliary proteins, Cell Signal, 18, 579, 10.1016/j.cellsig.2005.08.010 Ross, 2000, GTPase-activating proteins for heterotrimeric G proteins: regulators of G protein signaling (RGS) and RGS-like proteins, Annu Rev Biochem, 69, 795, 10.1146/annurev.biochem.69.1.795 Carman, 1999, Selective regulation of Galpha(q/11) by an RGS domain in the G protein-coupled receptor kinase, GRK2, J Biol Chem, 274, 34483, 10.1074/jbc.274.48.34483 Blumer, 2012, Group II activators of G-protein signaling and proteins containing a G-protein regulatory motif, Acta Physiol (Oxf), 204, 202, 10.1111/j.1748-1716.2011.02327.x Werts, 2011, How signaling between cells can orient a mitotic spindle, Semin Cell Dev Biol, 22, 842, 10.1016/j.semcdb.2011.07.011 Morin, 2011, Mitotic spindle orientation in asymmetric and symmetric cell divisions during animal development, Dev Cell, 21, 102, 10.1016/j.devcel.2011.06.012 Hewavitharana, 2012, Non-canonical signaling and localizations of heterotrimeric G proteins, Cell Signal, 24, 25, 10.1016/j.cellsig.2011.08.014 Chidiac, 1998, Rethinking receptor-G protein-effector interactions, Biochem Pharmacol, 55, 549, 10.1016/S0006-2952(97)00361-4 Graeser, 1993, Compartmentation of receptors and guanine nucleotide-binding proteins in NG108-15 cells: lack of cross-talk in agonist binding among the alpha 2-adrenergic, muscarinic, and opiate receptors, Mol Pharmacol, 43, 434 Kleuss, 1992, Different beta-subunits determine G-protein interaction with transmembrane receptors, Nature, 358, 424, 10.1038/358424a0 Kleuss, 1993, Selectivity in signal transduction determined by gamma subunits of heterotrimeric G proteins, Science, 259, 832, 10.1126/science.8094261 Kleuss, 1991, Assignment of G-protein subtypes to specific receptors inducing inhibition of calcium currents, Nature, 353, 43, 10.1038/353043a0 Rodbell, 1997, The complex regulation of receptor-coupled G-proteins, Adv Enzyme Regul, 37, 427, 10.1016/S0065-2571(96)00020-9 Boivin, 2008, G protein-coupled receptors in and on the cell nucleus: a new signaling paradigm?, J Recept Signal Transduct Res, 28, 15, 10.1080/10799890801941889 Hein, 2009, Coupling mode of receptors and G proteins, Naunyn Schmiedebergs Arch Pharmacol, 379, 435, 10.1007/s00210-008-0383-7 Lambert, 2008, Dissociation of heterotrimeric g proteins in cells, Sci Signal, 1, re5, 10.1126/scisignal.125re5 Scott, 2009, Cell signaling in space and time: where proteins come together and when they're apart, Science, 326, 1220, 10.1126/science.1175668 Welch, 2010, Networking with AKAPs: context-dependent regulation of anchored enzymes, Mol Interv, 10, 86, 10.1124/mi.10.2.6 Magalhaes, 2012, Regulation of GPCR activity, trafficking and localization by GPCR-interacting proteins, Br J Pharmacol, 165, 1717, 10.1111/j.1476-5381.2011.01552.x Suh, 2001, The roles of PDZ-containing proteins in PLC-beta-mediated signaling, Biochem Biophys Res Commun, 288, 1, 10.1006/bbrc.2001.5710 Greenwald, 2011, Further assessment of the clinically effective dose range of etoricoxib: a randomized, double-blinded, placebo-controlled trial in rheumatoid arthritis, Curr Med Res Opin, 27, 2033, 10.1185/03007995.2011.614935 Gazi, 2002, Formation of oligomers by G protein-coupled receptors, Curr Opin Drug Discov Devel, 5, 756 Bindslev, 2004, A homotropic two-state model and auto-antagonism, BMC Pharmacol, 4, 11, 10.1186/1471-2210-4-11 Smith, 2010, Allostery at G protein-coupled receptor homo- and heteromers: uncharted pharmacological landscapes, Pharmacol Rev, 62, 701, 10.1124/pr.110.002667 Park, 2004, Oligomerization of G protein-coupled receptors: past, present, and future, Biochemistry, 43, 15643, 10.1021/bi047907k Marshall, 1999, GABAB receptors—the first 7TM heterodimers, Trends Pharmacol Sci, 20, 396, 10.1016/S0165-6147(99)01383-8 Lu, 1996, Identification of the cysteine residues involved in the class I disulfide bonds of the human insulin receptor: properties of insulin receptor monomers, Mol Biol Cell, 7, 679, 10.1091/mbc.7.5.679 Chi, 2010, Transactivation of PDGFRbeta by dopamine D4 receptor does not require PDGFRbeta dimerization, Mol Brain, 3, 22, 10.1186/1756-6606-3-22 Whorton, 2007, A monomeric G protein-coupled receptor isolated in a high-density lipoprotein particle efficiently activates its G protein, Proc Natl Acad Sci USA, 104, 7682, 10.1073/pnas.0611448104 Ilkaeva, 2002, Mutations in the carboxyl-terminal domain of phospholipase C-beta 1 delineate the dimer interface and a potential Galphaq interaction site, J Biol Chem, 277, 4294, 10.1074/jbc.M109612200 Cooper, 2006, Higher-order organization and regulation of adenylyl cyclases, Trends Pharmacol Sci, 27, 426, 10.1016/j.tips.2006.06.002 Chidiac, 1992, Effects of adenyl nucleotides and carbachol on cooperative interactions among G proteins, Biochemistry, 31, 10908, 10.1021/bi00159a035 Gold, 2011, Architecture and dynamics of an A-kinase anchoring protein 79 (AKAP79) signaling complex, Proc Natl Acad Sci USA, 108, 6426, 10.1073/pnas.1014400108 Hepler, 1997, RGS4 and GAIP are GTPase-activating proteins for Gq alpha and block activation of phospholipase C beta by gamma-thio-GTP-Gq alpha, Proc Natl Acad Sci USA, 94, 428, 10.1073/pnas.94.2.428 Berman, 1996, GAIP and RGS4 are GTPase-activating proteins for the Gi subfamily of G protein alpha subunits, Cell, 86, 445, 10.1016/S0092-8674(00)80117-8 Natochin, 2001, Inhibition of GDP/GTP exchange on G alpha subunits by proteins containing G-protein regulatory motifs, Biochemistry, 40, 5322, 10.1021/bi015505w Oner, 2010, Receptor-regulated interaction of activator of G-protein signaling-4 and Galphai, J Biol Chem, 285, 20588, 10.1074/jbc.C109.088070 Roy, 2006, Up-regulation of endogenous RGS2 mediates cross-desensitization between Gs and Gq signaling in osteoblasts, J Biol Chem, 281, 32684, 10.1074/jbc.M604416200 Chatterjee, 1997, A truncated form of RGS3 negatively regulates G protein-coupled receptor stimulation of adenylyl cyclase and phosphoinositide phospholipase C, J Biol Chem, 272, 15481, 10.1074/jbc.272.24.15481 Johnson, 2002, Functional characterization of the G protein regulator RGS13, J Biol Chem, 277, 16768, 10.1074/jbc.M200751200 Scheschonka, 2000, RGS3 is a GTPase-activating protein for g(ialpha) and g(qalpha) and a potent inhibitor of signaling by GTPase-deficient forms of g(qalpha) and g(11alpha), Mol Pharmacol, 58, 719, 10.1124/mol.58.4.719 Roy, 2003, Recruitment of RGS2 and RGS4 to the plasma membrane by G proteins and receptors reflects functional interactions, Mol Pharmacol, 64, 587, 10.1124/mol.64.3.587 Heximer, 2001, Mechanisms governing subcellular localization and function of human RGS2, J Biol Chem, 276, 14195, 10.1074/jbc.M009942200 Gu, 2007, Unique hydrophobic extension of the RGS2 amphipathic helix domain imparts increased plasma membrane binding and function relative to other RGS R4/B subfamily members, J Biol Chem, 282, 33064, 10.1074/jbc.M702685200 Wang, 1997, A GTPase-activating protein for the G protein Galphaz. Identification, purification, and mechanism of action, J Biol Chem, 272, 5732, 10.1074/jbc.272.9.5732 Tang, 2006, Gbetagamma inhibits Galpha GTPase-activating proteins by inhibition of Galpha-GTP binding during stimulation by receptor, J Biol Chem, 281, 4746, 10.1074/jbc.M510573200 Mukhopadhyay, 1999, Rapid GTP binding and hydrolysis by G(q) promoted by receptor and GTPase-activating proteins, Proc Natl Acad Sci USA, 96, 9539, 10.1073/pnas.96.17.9539 Cladman, 2002, Characterization and comparison of RGS2 and RGS4 as GTPase-activating proteins for m2 muscarinic receptor-stimulated G(i), Mol Pharmacol, 62, 654, 10.1124/mol.62.3.654 Mao, 2004, RGS17/RGSZ2, a novel regulator of Gi/o, Gz, and Gq signaling, J Biol Chem, 279, 26314, 10.1074/jbc.M401800200 Biddlecome, 1996, Regulation of phospholipase C-beta1 by Gq and m1 muscarinic cholinergic receptor. Steady-state balance of receptor-mediated activation and GTPase-activating protein-promoted deactivation, J Biol Chem, 271, 7999, 10.1074/jbc.271.14.7999 Berstein, 1992, Phospholipase C-beta 1 is a GTPase-activating protein for Gq/11, its physiologic regulator, Cell, 70, 411, 10.1016/0092-8674(92)90165-9 Min, 2012, RGS4 exerts inhibitory activities on the signaling of dopamine D2 receptor and D3 receptor through the N-terminal region, Pharmacol Res, 65, 213, 10.1016/j.phrs.2011.08.008 Zeng, 1998, The N-terminal domain of RGS4 confers receptor-selective inhibition of G protein signaling, J Biol Chem, 273, 34687, 10.1074/jbc.273.52.34687 Matsuzaki, 2011, Potent and selective inhibition of angiotensin AT1 receptor signaling by RGS2: roles of its N-terminal domain, Cell Signal, 23, 1041, 10.1016/j.cellsig.2011.01.023 Sandiford, 2010, Molecular organization of the complex between the muscarinic M3 receptor and the regulator of G protein signaling, Gbeta(5)-RGS7, Biochemistry, 49, 4998, 10.1021/bi100080p Chen, 2012, Neurabin scaffolding of adenosine receptor and RGS4 regulates anti-seizure effect of endogenous adenosine, J Neurosci, 32, 2683, 10.1523/JNEUROSCI.4125-11.2011 Wang, 2005, Spinophilin regulates Ca2+ signaling by binding the N-terminal domain of RGS2 and the third intracellular loop of G-protein-coupled receptors, Nat Cell Biol, 7, 405, 10.1038/ncb1237 Ruiz de Azua, 2012, Spinophilin as a novel regulator of M3 muscarinic receptor-mediated insulin release in vitro and in vivo, FASEB J, 26, 4275, 10.1096/fj.12-204644 Xu, 1999, RGS proteins determine signaling specificity of Gq-coupled receptors, J Biol Chem, 274, 3549, 10.1074/jbc.274.6.3549 Wang, 2002, Receptor-selective effects of endogenous RGS3 and RGS5 to regulate mitogen-activated protein kinase activation in rat vascular smooth muscle cells, J Biol Chem, 277, 24949, 10.1074/jbc.M203802200 Saitoh, 2002, Alternative splicing of RGS8 gene determines inhibitory function of receptor type-specific Gq signaling, Proc Natl Acad Sci USA, 99, 10138, 10.1073/pnas.152085999 Cho, 2003, The aorta and heart differentially express RGS (regulators of G-protein signaling) proteins that selectively regulate sphingosine 1-phosphate, angiotensin II and endothelin-1 signaling, Biochem J, 371, 973, 10.1042/bj20021769 Benians, 2005, Regulators of G-protein signaling form a quaternary complex with the agonist, receptor, and G-protein. A novel explanation for the acceleration of signaling activation kinetics, J Biol Chem, 280, 13383, 10.1074/jbc.M410163200 Schneider, 2009, Histamine H(4) receptor-RGS fusion proteins expressed in Sf9 insect cells: a sensitive and reliable approach for the functional characterization of histamine H(4) receptor ligands, Biochem Pharmacol, 78, 607, 10.1016/j.bcp.2009.05.015 Abramow-Newerly, 2006, Modulation of subfamily B/R4 RGS protein function by 14-3-3 proteins, Cell Signal, 18, 2209, 10.1016/j.cellsig.2006.05.011 Anger, 2004, Differential contribution of GTPase activation and effector antagonism to the inhibitory effect of RGS proteins on Gq-mediated signaling in vivo, J Biol Chem, 279, 3906, 10.1074/jbc.M309496200 Bernstein, 2004, RGS2 binds directly and selectively to the M1 muscarinic acetylcholine receptor third intracellular loop to modulate Gq/11alpha signaling, J Biol Chem, 279, 21248, 10.1074/jbc.M312407200 Neer, 1995, Heterotrimeric G proteins: organizers of transmembrane signals, Cell, 80, 249, 10.1016/0092-8674(95)90407-7 Kitatsuji, 2007, Molecular basis of guanine nucleotide dissociation inhibitor activity of human neuroglobin by chemical cross-linking and mass spectrometry, J Mol Biol, 368, 150, 10.1016/j.jmb.2007.02.002 Wakasugi, 2003, Oxidized human neuroglobin acts as a heterotrimeric Galpha protein guanine nucleotide dissociation inhibitor, J Biol Chem, 278, 36505, 10.1074/jbc.M305519200 Takesono, 1999, Receptor-independent activators of heterotrimeric G-protein signaling pathways, J Biol Chem, 274, 33202, 10.1074/jbc.274.47.33202 Cismowski, 1999, Genetic screens in yeast to identify mammalian nonreceptor modulators of G-protein signaling, Nat Biotechnol, 17, 878, 10.1038/12867 Willard, 2004, Return of the GDI: the GoLoco motif in cell division, Annu Rev Biochem, 73, 925, 10.1146/annurev.biochem.73.011303.073756 Granderath, 1999, loco encodes an RGS protein required for Drosophila glial differentiation, Development, 126, 1781, 10.1242/dev.126.8.1781 Siderovski, 1999, The GoLoco motif: a Galphai/o binding motif and potential guanine-nucleotide exchange factor, Trends Biochem Sci, 24, 340, 10.1016/S0968-0004(99)01441-3 Mochizuki, 1996, Identification and cDNA cloning of a novel human mosaic protein, LGN, based on interaction with G alpha i2, Gene, 181, 39, 10.1016/S0378-1119(96)00456-8 Ponting, 1999, Raf-like Ras/Rap-binding domains in RGS12- and still-life-like signaling proteins, J Mol Med (Berl), 77, 695, 10.1007/s001099900054 Blumer, 2005, AGS proteins: receptor-independent activators of G-protein signaling, Trends Pharmacol Sci, 26, 470 Natochin, 2000, AGS3 inhibits GDP dissociation from galpha subunits of the Gi family and rhodopsin-dependent activation of transducin, J Biol Chem, 275, 40981, 10.1074/jbc.M006478200 Kimple, 2002, Structural determinants for GoLoco-induced inhibition of nucleotide release by Galpha subunits, Nature, 416, 878, 10.1038/416878a Siderovski, 2005, The GAPs, GEFs, and GDIs of heterotrimeric G-protein alpha subunits, Int J Biol Sci, 1, 51, 10.7150/ijbs.1.51 Bernard, 2001, Selective interaction of AGS3 with G-proteins and the influence of AGS3 on the activation state of G-proteins, J Biol Chem, 276, 1585, 10.1074/jbc.M005291200 Ghosh, 2003, Receptor- and nucleotide exchange-independent mechanisms for promoting G protein subunit dissociation, J Biol Chem, 278, 34747, 10.1074/jbc.C300271200 Mittal, 2006, Biochemical characterization of RGS14: RGS14 activity towards G-protein alpha subunits is independent of its binding to Rap2A, Biochem J, 394, 309, 10.1042/BJ20051086 Webb, 2005, D2 dopamine receptor activation of potassium channels is selectively decoupled by Galpha-specific GoLoco motif peptides, J Neurochem, 92, 1408, 10.1111/j.1471-4159.2004.02997.x Sanada, 2005, G protein betagamma subunits and AGS3 control spindle orientation and asymmetric cell fate of cerebral cortical progenitors, Cell, 122, 119, 10.1016/j.cell.2005.05.009 Giguere, 2012, G-protein signaling modulator-3 regulates heterotrimeric G-protein dynamics through dual association with Gbeta and Galphai protein subunits, J Biol Chem, 287, 4863, 10.1074/jbc.M111.311712 Wiser, 2006, Modulation of basal and receptor-induced GIRK potassium channel activity and neuronal excitability by the mammalian PINS homolog LGN, Neuron, 50, 561, 10.1016/j.neuron.2006.03.046 Kinoshita-Kawada, 2004, A Purkinje cell specific GoLoco domain protein, L7/Pcp-2, modulates receptor-mediated inhibition of Cav2.1 Ca2+ channels in a dose-dependent manner, Brain Res Mol Brain Res, 132, 73, 10.1016/j.molbrainres.2004.09.007 Ma, 2003, Influence of cytosolic AGS3 on receptor–G protein coupling, Biochemistry, 42, 8085, 10.1021/bi034561p Oner, 2010, Regulation of the AGS3.G{alpha}i signaling complex by a seven-transmembrane span receptor, J Biol Chem, 285, 33949, 10.1074/jbc.M110.138073 Zhao, 2010, The proline-rich N-terminal domain of G18 exhibits a novel G protein regulatory function, J Biol Chem, 285, 9008, 10.1074/jbc.M109.057174 Thomas, 2008, Ric-8A catalyzes guanine nucleotide exchange on G alphai1 bound to the GPR/GoLoco exchange inhibitor AGS3, J Biol Chem, 283, 23150, 10.1074/jbc.M802422200 Blumer, 2007, Mechanistic pathways and biological roles for receptor-independent activators of G-protein signaling, Pharmacol Ther, 113, 488, 10.1016/j.pharmthera.2006.11.001 Shippenberg, 1997, Sensitization to the behavioral effects of cocaine: modulation by dynorphin and kappa-opioid receptor agonists, Pharmacol Biochem Behav, 57, 449, 10.1016/S0091-3057(96)00450-9 Bowers, 2004, Activator of G protein signaling 3: a gatekeeper of cocaine sensitization and drug seeking, Neuron, 42, 269, 10.1016/S0896-6273(04)00159-X Bowers, 2010, Activators of G-protein signaling 3: a drug addiction molecular gateway, Behav Pharmacol, 21, 500, 10.1097/FBP.0b013e32833dcfa5 Parks, 1998, Increased anxiety of mice lacking the serotonin1A receptor, Proc Natl Acad Sci USA, 95, 10734, 10.1073/pnas.95.18.10734 Chan, 2011, Ric-8B is a GTP-dependent G protein alphas guanine nucleotide exchange factor, J Biol Chem, 286, 19932, 10.1074/jbc.M110.163675 Garcia-Marcos, 2009, GIV is a nonreceptor GEF for G alpha i with a unique motif that regulates Akt signaling, Proc Natl Acad Sci USA, 106, 3178, 10.1073/pnas.0900294106 Cismowski, 2000, Activation of heterotrimeric G-protein signaling by a ras-related protein. Implications for signal integration, J Biol Chem, 275, 23421, 10.1074/jbc.C000322200 Strittmatter, 1991, An intracellular guanine nucleotide release protein for G0. GAP-43 stimulates isolated alpha subunits by a novel mechanism, J Biol Chem, 266, 22465, 10.1016/S0021-9258(18)54595-6 Natochin, 2005, Characterization of the G alpha(s) regulator cysteine string protein, J Biol Chem, 280, 30236, 10.1074/jbc.M500722200 Kroslak, 2001, Human phosphatidylethanolamine-binding protein facilitates heterotrimeric G protein-dependent signaling, J Biol Chem, 276, 39772, 10.1074/jbc.M106991200 Nishimoto, 1993, Alzheimer amyloid protein precursor complexes with brain GTP-binding protein G(o), Nature, 362, 75, 10.1038/362075a0 Smine, 1998, Regulation of brain G-protein go by Alzheimer's disease gene presenilin-1, J Biol Chem, 273, 16281, 10.1074/jbc.273.26.16281 Lee, 2008, Coactivation of G protein signaling by cell-surface receptors and an intracellular exchange factor, Curr Biol, 18, 211, 10.1016/j.cub.2008.01.007 Garcia-Marcos, 2011, G Protein binding sites on Calnuc (nucleobindin 1) and NUCB2 (nucleobindin 2) define a new class of G(alpha)i-regulatory motifs, J Biol Chem, 286, 28138, 10.1074/jbc.M110.204099 Hagemann, 2007, E2F8 is a nonreceptor activator of heterotrimeric G proteins, J Mol Signal, 2, 3, 10.1186/1750-2187-2-3 Sato, 1996, Characterization of a G-protein activator in the neuroblastoma-glioma cell hybrid NG108-15, J Biol Chem, 271, 30052, 10.1074/jbc.271.47.30052 Patel, 2004, Single transmembrane spanning heterotrimeric g protein-coupled receptors and their signaling cascades, Pharmacol Rev, 56, 371, 10.1124/pr.56.3.4 Marty, 2010, Heterotrimeric G protein signaling outside the realm of seven transmembrane domain receptors, Mol Pharmacol, 78, 12, 10.1124/mol.110.063453 Pyne, 2012, Targeting sphingosine kinase 1 in cancer, Adv Biol Regul, 52, 31, 10.1016/j.advenzreg.2011.07.001 El-Shewy, 2009, Insulin-like growth factor-2/mannose-6 phosphate receptors, Vitam Horm, 80, 667, 10.1016/S0083-6729(08)00624-9 Miller, 1996, A genetic selection for Caenorhabditis elegans synaptic transmission mutants, Proc Natl Acad Sci USA, 93, 12593, 10.1073/pnas.93.22.12593 Hinrichs, 2012, Ric-8: different cellular roles for a heterotrimeric G-protein GEF, J Cell Biochem, 113, 2797, 10.1002/jcb.24162 Tall, 2003, Mammalian Ric-8A (synembryn) is a heterotrimeric Galpha protein guanine nucleotide exchange factor, J Biol Chem, 278, 8356, 10.1074/jbc.M211862200 Nishimura, 2006, Ric-8A potentiates Gq-mediated signal transduction by acting downstream of G protein-coupled receptor in intact cells, Genes Cells, 11, 487, 10.1111/j.1365-2443.2006.00959.x Klattenhoff, 2003, Human brain synembryn interacts with Gsalpha and Gqalpha and is translocated to the plasma membrane in response to isoproterenol and carbachol, J Cell Physiol, 195, 151, 10.1002/jcp.10300 Von Dannecker, 2005, Ric-8B, an olfactory putative GTP exchange factor, amplifies signal transduction through the olfactory-specific G-protein Galphaolf, J Neurosci, 25, 3793, 10.1523/JNEUROSCI.4595-04.2005 Wang, 2007, Regulation of type V adenylate cyclase by Ric8a, a guanine nucleotide exchange factor, Biochem J, 406, 383, 10.1042/BJ20070512 Amoureux, 2012, NCAM180 regulates Ric8A membrane localization and potentiates beta-adrenergic response, PLoS One, 7, e32216, 10.1371/journal.pone.0032216 Hampoelz, 2005, Drosophila Ric-8 is essential for plasma-membrane localization of heterotrimeric G proteins, Nat Cell Biol, 7, 1099, 10.1038/ncb1318 Gabay, 2011, Ric-8 proteins are molecular chaperones that direct nascent G protein alpha subunit membrane association, Sci Signal, 4, ra79, 10.1126/scisignal.2002223 Tonissoo, 2010, Nucleotide exchange factor RIC-8 is indispensable in mammalian early development, Dev Dyn, 239, 3404, 10.1002/dvdy.22480 Nagai, 2010, Ric-8B stabilizes the alpha subunit of stimulatory G protein by inhibiting its ubiquitination, J Biol Chem, 285, 11114, 10.1074/jbc.M109.063313 Von Dannecker, 2006, Ric-8B promotes functional expression of odorant receptors, Proc Natl Acad Sci USA, 103, 9310, 10.1073/pnas.0600697103 Chan, 2011, Purification of heterotrimeric G protein alpha subunits by GST-Ric-8 association: primary characterization of purified G alpha(olf), J Biol Chem, 286, 2625, 10.1074/jbc.M110.178897 Hofler, 2011, AGS-3 alters Caenorhabditis elegans behavior after food deprivation via RIC-8 activation of the neural G protein G alphao, J Neurosci, 31, 11553, 10.1523/JNEUROSCI.2072-11.2011 Digby, 2008, Differential dissociation of G protein heterotrimers, J Physiol, 586, 3325, 10.1113/jphysiol.2008.153965 Ghosh, 2008, Activation of Galphai3 triggers cell migration via regulation of GIV, J Cell Biol, 182, 381, 10.1083/jcb.200712066 Garcia-Marcos, 2012, Functional characterization of the guanine nucleotide exchange factor (GEF) motif of GIV protein reveals a threshold effect in signaling, Proc Natl Acad Sci USA, 109, 1961, 10.1073/pnas.1120538109 Ghosh, 2011, GIV/Girdin is a rheostat that fine-tunes growth factor signals during tumor progression, Cell Adh Migr, 5, 237, 10.4161/cam.5.3.15909 Hill, 2009, The cationic region of Rhes mediates its interactions with specific Gbeta subunits, Cell Physiol Biochem, 23, 1, 10.1159/000204075 Vargiu, 2004, The small GTP-binding protein, Rhes, regulates signal transduction from G protein-coupled receptors, Oncogene, 23, 559, 10.1038/sj.onc.1207161 Graham, 2002, Dexras1/AGS-1 inhibits signal transduction from the Gi-coupled formyl peptide receptor to Erk-1/2 MAP kinases, J Biol Chem, 277, 10876, 10.1074/jbc.M110397200 Sato, 2006, Accessory proteins for G proteins: partners in signaling, Annu Rev Pharmacol Toxicol, 46, 151, 10.1146/annurev.pharmtox.46.120604.141115 Harrison, 2011, Rhes and AGS1/Dexras1 affect signaling by dopamine D1 receptors through adenylyl cyclase, J Neurosci Res, 89, 874, 10.1002/jnr.22604 Hiskens, 2005, Specific in vivo binding of activator of G protein signaling 1 to the Gbeta1 subunit, Biochem Biophys Res Commun, 337, 1038, 10.1016/j.bbrc.2005.09.149 Fang, 2000, Dexras1: a G protein specifically coupled to neuronal nitric oxide synthase via CAPON, Neuron, 28, 183, 10.1016/S0896-6273(00)00095-7 Bang, 2012, Striatum specific protein, Rhes regulates AKT pathway, Neurosci Lett, 521, 142, 10.1016/j.neulet.2012.05.073 Nguyen, 2005, Dexras1 blocks receptor-mediated heterologous sensitization of adenylyl cyclase 1, Biochem Biophys Res Commun, 332, 913, 10.1016/j.bbrc.2005.05.041 Takesono, 2002, Activator of G-protein signaling 1 blocks GIRK channel activation by a G-protein-coupled receptor: apparent disruption of receptor signaling complexes, J Biol Chem, 277, 13827, 10.1074/jbc.M201064200 Thapliyal, 2008, The monomeric G proteins AGS1 and Rhes selectively influence Galphai-dependent signaling to modulate N-type (CaV2.2) calcium channels, Am J Physiol Cell Physiol, 295, C1417, 10.1152/ajpcell.00341.2008 Strittmatter, 1993, GAP-43 augments G protein-coupled receptor transduction in Xenopus laevis oocytes, Proc Natl Acad Sci USA, 90, 5327, 10.1073/pnas.90.11.5327 Afshar, 2004, RIC-8 is required for GPR-1/2-dependent Galpha function during asymmetric division of C. elegans embryos, Cell, 119, 219, 10.1016/j.cell.2004.09.026 Couwenbergs, 2004, Control of embryonic spindle positioning and Galpha activity by C. elegans RIC-8, Curr Biol, 14, 1871, 10.1016/j.cub.2004.09.059 David, 2005, Drosophila Ric-8 regulates Galphai cortical localization to promote Galphai-dependent planar orientation of the mitotic spindle during asymmetric cell division, Nat Cell Biol, 7, 1083, 10.1038/ncb1319 Tall, 2005, Resistance to inhibitors of cholinesterase 8A catalyzes release of Galphai-GTP and nuclear mitotic apparatus protein (NuMA) from NuMA/LGN/Galphai-GDP complexes, Proc Natl Acad Sci USA, 102, 16584, 10.1073/pnas.0508306102 Vellano, 2011, Activation of the regulator of G protein signaling 14-Galphai1-GDP signaling complex is regulated by resistance to inhibitors of cholinesterase-8A, Biochemistry, 50, 752, 10.1021/bi101910n Hollinger, 2001, RGS14 is a bifunctional regulator of Galphai/o activity that exists in multiple populations in brain, J Neurochem, 79, 941, 10.1046/j.1471-4159.2001.00629.x