gi go gtp binding protein alpha subunits


Summary: A family of heterotrimeric GTP-binding protein alpha subunits that were originally identified by their ability to inhibit ADENYLYL CYCLASES. Members of this family can couple to beta and gamma G-protein subunits that activate POTASSIUM CHANNELS. The Gi-Go part of the name is also spelled Gi/Go.

Top Publications

  1. Baker J, Hill S. A comparison of the antagonist affinities for the Gi- and Gs-coupled states of the human adenosine A1-receptor. J Pharmacol Exp Ther. 2007;320:218-28 pubmed
    ..This was true even when the receptor was shown, in the same assay, to exist in two different conformational states coupled to two different G proteins. ..
  2. Yoon C, Hong B, Moon H, Lim S, Suh P, Kim Y, et al. Sphingosine-1-phosphate promotes lymphangiogenesis by stimulating S1P1/Gi/PLC/Ca2+ signaling pathways. Blood. 2008;112:1129-38 pubmed publisher
    ..Our results suggest that S1P is the first lymphangiogenic bioactive lipid to be identified, and that S1P and its receptors might serve as new therapeutic targets against inflammatory diseases and lymphatic metastasis in tumors. ..
  3. Ruan H, Mitchell S, Vainoriene M, Lou Q, Xie L, Ren S, et al. Gi alpha 1-mediated cardiac electrophysiological remodeling and arrhythmia in hypertrophic cardiomyopathy. Circulation. 2007;116:596-605 pubmed
  4. Bringmann H, Cowan C, Kong J, Hyman A. LET-99, GOA-1/GPA-16, and GPR-1/2 are required for aster-positioned cytokinesis. Curr Biol. 2007;17:185-91 pubmed
    ..We conclude that LET-99 and the G proteins define a molecular pathway required for aster-positioned cytokinesis. ..
  5. Ghosh P, Garcia Marcos M, Bornheimer S, Farquhar M. Activation of Galphai3 triggers cell migration via regulation of GIV. J Cell Biol. 2008;182:381-93 pubmed publisher
  6. Blumer J, Kuriyama R, Gettys T, Lanier S. The G-protein regulatory (GPR) motif-containing Leu-Gly-Asn-enriched protein (LGN) and Gialpha3 influence cortical positioning of the mitotic spindle poles at metaphase in symmetrically dividing mammalian cells. Eur J Cell Biol. 2006;85:1233-40 pubmed
  7. Camerer E, Regard J, Cornelissen I, Srinivasan Y, Duong D, Palmer D, et al. Sphingosine-1-phosphate in the plasma compartment regulates basal and inflammation-induced vascular leak in mice. J Clin Invest. 2009;119:1871-9 pubmed
    ..Our results suggest that the blood communicates with blood vessels via plasma S1P to maintain vascular integrity and regulate vascular leak. This pathway prevents lethal responses to leak-inducing mediators in mouse models. ..
  8. Rusinova R, Mirshahi T, Logothetis D. Specificity of Gbetagamma signaling to Kir3 channels depends on the helical domain of pertussis toxin-sensitive Galpha subunits. J Biol Chem. 2007;282:34019-30 pubmed
    ..These results implicate the helical domain of Galpha(i) proteins as a critical determinant of Gbetagamma signaling specificity. ..
  9. Feigin M, Malbon C. RGS19 regulates Wnt-beta-catenin signaling through inactivation of Galpha(o). J Cell Sci. 2007;120:3404-14 pubmed
    ..However, knockdown of RGS19 by siRNA suppressed canonical Wnt signaling, suggesting a complex role for RGS19 in regulating the ability of Wnt3a to signal to the level of beta-catenin and gene transcription. ..

More Information


  1. Sammond D, Eletr Z, Purbeck C, Kimple R, Siderovski D, Kuhlman B. Structure-based protocol for identifying mutations that enhance protein-protein binding affinities. J Mol Biol. 2007;371:1392-404 pubmed
    ..Of the eight mutations identified, five were accurately predicted to increase binding affinity, further validating the method as a useful tool to increase protein-protein binding affinities. ..
  2. Shi G, Jin L, Andres D. Pituitary adenylate cyclase-activating polypeptide 38-mediated Rin activation requires Src and contributes to the regulation of HSP27 signaling during neuronal differentiation. Mol Cell Biol. 2008;28:4940-51 pubmed publisher
  3. Shu F, Ramineni S, Amyot W, Hepler J. Selective interactions between Gi alpha1 and Gi alpha3 and the GoLoco/GPR domain of RGS14 influence its dynamic subcellular localization. Cell Signal. 2007;19:163-76 pubmed
    ..These findings highlight the importance of the GoLoco/GPR domain and its interactions with Gi alpha1/3 in determining RGS14 subcellular localization and linked functions. ..
  4. Regard J, Kataoka H, Cano D, Camerer E, Yin L, Zheng Y, et al. Probing cell type-specific functions of Gi in vivo identifies GPCR regulators of insulin secretion. J Clin Invest. 2007;117:4034-43 pubmed
  5. Garcia Marcos M, Ghosh P, Farquhar M. GIV is a nonreceptor GEF for G alpha i with a unique motif that regulates Akt signaling. Proc Natl Acad Sci U S A. 2009;106:3178-83 pubmed publisher
  6. Ferris J, Ge H, Liu L, Roman G. G(o) signaling is required for Drosophila associative learning. Nat Neurosci. 2006;9:1036-40 pubmed
    ..PTX expression also does not interact genetically with a rutabaga adenylyl cyclase loss-of-function mutation. Thus, G(o) defines a new signaling pathway required in mushroom body neurons for the formation of associative memory. ..
  7. Cho H, Kehrl J. Localization of Gi alpha proteins in the centrosomes and at the midbody: implication for their role in cell division. J Cell Biol. 2007;178:245-55 pubmed
    ..These results suggest that G(ialpha) proteins and their regulators at these sites may play essential roles during mammalian cell division. ..
  8. Katanaev V, Ponzielli R, Semeriva M, Tomlinson A. Trimeric G protein-dependent frizzled signaling in Drosophila. Cell. 2005;120:111-22 pubmed
    ..Thus, Go is likely part of a trimeric G protein complex that directly transduces Fz signals from the membrane to downstream components. ..
  9. Hampoelz B, Hoeller O, Bowman S, Dunican D, Knoblich J. Drosophila Ric-8 is essential for plasma-membrane localization of heterotrimeric G proteins. Nat Cell Biol. 2005;7:1099-105 pubmed
    ..Our results indicate a model in which both receptor-dependent and receptor-independent G-protein functions are executed at the plasma membrane and require the Ric-8 protein. ..
  10. Germack R, Dickenson J. Induction of beta3-adrenergic receptor functional expression following chronic stimulation with noradrenaline in neonatal rat cardiomyocytes. J Pharmacol Exp Ther. 2006;316:392-402 pubmed
  11. Tall G, Gilman A. 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 U S A. 2005;102:16584-9 pubmed
  12. He J, Gomes I, Nguyen T, Jayaram G, Ram P, Devi L, et al. The G alpha(o/i)-coupled cannabinoid receptor-mediated neurite outgrowth involves Rap regulation of Src and Stat3. J Biol Chem. 2005;280:33426-34 pubmed
    ..Overall, this study demonstrated that G alpha(o/i)-coupled CB1R triggers neurite outgrowth in Neuro-2A through the activation of a signaling network containing two pathways that bifurcate at Src and converge at Stat3. ..
  13. Le Niculescu H, Niesman I, Fischer T, DeVries L, Farquhar M. Identification and characterization of GIV, a novel Galpha i/s-interacting protein found on COPI, endoplasmic reticulum-Golgi transport vesicles. J Biol Chem. 2005;280:22012-20 pubmed
  14. Gibson S, Gilman A. Gialpha and Gbeta subunits both define selectivity of G protein activation by alpha2-adrenergic receptors. Proc Natl Acad Sci U S A. 2006;103:212-7 pubmed
    ..The molecular properties of each Gialpha, Gbeta, and alpha2-adrenergic receptor subtype influence signaling efficiency for the alpha2-adrenergic receptor-mediated signaling pathway. ..
  15. McCudden C, Willard F, Kimple R, Johnston C, Hains M, Jones M, et al. G alpha selectivity and inhibitor function of the multiple GoLoco motif protein GPSM2/LGN. Biochim Biophys Acta. 2005;1745:254-64 pubmed
    ..Consistent with our binding studies, the GDI activity of GPSM2 GoLoco motifs on Galpha(o) was significantly lower than that toward Galpha(i1), suggesting that the in vivo targets of GPSM2 are most likely to be Galpha(i)-subunits. ..
  16. Tong H, Bernstein D, Murphy E, Steenbergen C. The role of beta-adrenergic receptor signaling in cardioprotection. FASEB J. 2005;19:983-5 pubmed
    ..These data show an important role for beta2-AR in cardioprotection and support the novel hypothesis that preconditioning involves switching of beta2-AR coupling from Gs to Gi. ..
  17. Han S, Moratz C, Huang N, Kelsall B, Cho H, Shi C, et al. Rgs1 and Gnai2 regulate the entrance of B lymphocytes into lymph nodes and B cell motility within lymph node follicles. Immunity. 2005;22:343-54 pubmed
    ..These results demonstrate opposing roles for Rgs1 and Gnai2 in B cell trafficking into and within lymph nodes. ..
  18. He J, Balijepalli R, Haworth R, Kamp T. Crosstalk of beta-adrenergic receptor subtypes through Gi blunts beta-adrenergic stimulation of L-type Ca2+ channels in canine heart failure. Circ Res. 2005;97:566-73 pubmed
    ..These results have implications for optimizing the use of beta-AR drugs in HF. ..
  19. Frank M, Thümer L, Lohse M, Bünemann M. G Protein activation without subunit dissociation depends on a G{alpha}(i)-specific region. J Biol Chem. 2005;280:24584-90 pubmed
    ..The discovery of subtype-selective mechanisms of G protein activation illustrates that G protein subfamilies have specific mechanisms of activation that may provide a previously unknown basis for G protein signaling specificity. ..
  20. Van Kolen K, Dautzenberg F, Verstraeten K, Royaux I, de Hoogt R, Gutknecht E, et al. Corticotropin releasing factor-induced ERK phosphorylation in AtT20 cells occurs via a cAMP-dependent mechanism requiring EPAC2. Neuropharmacology. 2010;58:135-44 pubmed publisher
    ..Further research will provide more insight in the role of EPAC2 in CRF signalling. ..
  21. Brighton P, Wise A, Dass N, Willars G. Paradoxical behavior of neuromedin U in isolated smooth muscle cells and intact tissue. J Pharmacol Exp Ther. 2008;325:154-64 pubmed publisher
    ..The reason for this discrepancy is presently unknown. ..
  22. Al Shawaf E, Naylor J, Taylor H, Riches K, Milligan C, O Regan D, et al. Short-term stimulation of calcium-permeable transient receptor potential canonical 5-containing channels by oxidized phospholipids. Arterioscler Thromb Vasc Biol. 2010;30:1453-9 pubmed publisher
    ..Stimulation of calcium-permeable TRPC5-containing channels may be an early event in cellular responses to oxidized phospholipids that couples to cell migration and requires an unidentified G protein-coupled receptor. ..
  23. Bosier B, Hermans E, Lambert D. Differential modulation of AP-1- and CRE-driven transcription by cannabinoid agonists emphasizes functional selectivity at the CB1 receptor. Br J Pharmacol. 2008;155:24-33 pubmed publisher
    ..This could reflect activation of distinct subsets of Gi/o-proteins, supporting the concept of functional selectivity at CB1 receptors. ..
  24. Chakir K, Daya S, Aiba T, Tunin R, Dimaano V, Abraham T, et al. Mechanisms of enhanced beta-adrenergic reserve from cardiac resynchronization therapy. Circulation. 2009;119:1231-40 pubmed publisher
    ..The result is greater rest and sympathetic reserve despite reduced myocardial neurostimulation as components underlying its net benefit. ..
  25. Kim J, Kim Y, Ko J. CKbeta8/CCL23 and its isoform CKbeta8-1 induce up-regulation of cyclins via the G(i)/G(o) protein/PLC/PKCdelta/ERK leading to cell-cycle progression. Cytokine. 2010;50:42-9 pubmed publisher
    ..These results indicate that both CKbeta8 and CKbeta8-1 are involved in cell proliferation by modulating the cell cycle regulators. ..
  26. Cacanyiova S, Kristek F, Kunes J, Zicha J. The effects of pertussis toxin-treatment on integrated vasoactive response of vascular system in spontaneously hypertensive rats. Physiol Res. 2008;57:137-9 pubmed
  27. Wilson T, Nannuru K, Singh R. Cathepsin G recruits osteoclast precursors via proteolytic activation of protease-activated receptor-1. Cancer Res. 2009;69:3188-95 pubmed publisher
  28. Devine K, Smicun Y, Hope J, Fishman D. S1P induced changes in epithelial ovarian cancer proteolysis, invasion, and attachment are mediated by Gi and Rac. Gynecol Oncol. 2008;110:237-45 pubmed publisher
    ..Furthermore, this study illustrates that the net effect of S1P on each of these processes reflects a complex interplay of multiple GPCR pathways involving Gi and downstream Rac. ..
  29. Thomas C, Tall G, Adhikari A, Sprang S. Ric-8A catalyzes guanine nucleotide exchange on G alphai1 bound to the GPR/GoLoco exchange inhibitor AGS3. J Biol Chem. 2008;283:23150-60 pubmed publisher
    ..Galpha(i1) complex, even when present at very high concentrations. The action of Ric-8A on AGS3:Galpha(i1).GDP ensures unidirectional activation of Galpha subunits that cannot be reversed by AGS3. ..
  30. Nafisi H, Banihashemi B, Daigle M, Albert P. GAP1(IP4BP)/RASA3 mediates Galphai-induced inhibition of mitogen-activated protein kinase. J Biol Chem. 2008;283:35908-17 pubmed publisher
    ..Our results provide a novel mechanism for dopamine D2S-induced inhibition of ERK1/2 and indicate that RASA3 links Galphai proteins to inhibit Gq-induced Ras/ERK1/2 activation. ..
  31. Nesterov V, Katkova L, Baturina G, Solenov E, Ivanova L. [G(i) proteins in regulation of water permeability of the rat kidney collecting tube epithelium cell membrane]. Ross Fiziol Zh Im I M Sechenova. 2007;93:329-36 pubmed
    ..Clarification of the G(i)-proteins role in this process requires further investigation, but most likely they are involved in regulation of aquaporin transport and insertion into the cell membrane. ..
  32. Bartolomé R, Wright N, Molina Ortiz I, Sánchez Luque F, Teixido J. Activated G(alpha)13 impairs cell invasiveness through p190RhoGAP-mediated inhibition of RhoA activity. Cancer Res. 2008;68:8221-30 pubmed publisher
  33. Burgos Ramos E, Hervás Aguilar A, Puebla Jiménez L, Boyano Adánez M, Arilla Ferreiro E. Chronic but not acute intracerebroventricular administration of amyloid beta-peptide(25-35) decreases somatostatin content, adenylate cyclase activity, somatostatin-induced inhibition of adenylate cyclase activity, and adenylate cyclase I levels in t. J Neurosci Res. 2007;85:433-42 pubmed
  34. Zarbock A, Abram C, Hundt M, Altman A, Lowell C, Ley K. PSGL-1 engagement by E-selectin signals through Src kinase Fgr and ITAM adapters DAP12 and FcR gamma to induce slow leukocyte rolling. J Exp Med. 2008;205:2339-47 pubmed publisher
  35. Zemancíková A, Torok J, Zicha J, Kunes J. Inactivation of G(i) proteins by pertussis toxin diminishes the effectiveness of adrenergic stimuli in conduit arteries from spontaneously hypertensive rats. Physiol Res. 2008;57:299-302 pubmed
    ..These results indicate that PTX treatment markedly diminishes the effectiveness of adrenergic stimuli in vasculature of SHR. This could importantly affect BP regulation in genetic hypertension. ..
  36. Gerrits A, Koekman C, Yildirim C, Nieuwland R, Akkerman J. Insulin inhibits tissue factor expression in monocytes. J Thromb Haemost. 2009;7:198-205 pubmed publisher
    ..Insulin inhibits TF expression in monocytes and monocyte-derived microparticles through interference with G(i)alpha(2)-mediated cAMP suppression, which attenuates Ca(2+)-mediated TF synthesis. ..
  37. Berlin S, Keren Raifman T, Castel R, Rubinstein M, Dessauer C, Ivanina T, et al. G alpha(i) and G betagamma jointly regulate the conformations of a G betagamma effector, the neuronal G protein-activated K+ channel (GIRK). J Biol Chem. 2010;285:6179-85 pubmed publisher
    ..Our findings imply that G alpha(i/o) and the G alpha(i) betagamma heterotrimer can regulate a G betagamma effector both before and after activation by neurotransmitters. ..
  38. Michel N, Ganter K, Venzke S, Bitzegeio J, Fackler O, Keppler O. The Nef protein of human immunodeficiency virus is a broad-spectrum modulator of chemokine receptor cell surface levels that acts independently of classical motifs for receptor endocytosis and Galphai signaling. Mol Biol Cell. 2006;17:3578-90 pubmed
    ..Nef uses a mechanism that is distinct from well-established pathways orchestrating CKR metabolism and offers an interesting tool to study the multifaceted biology of CKRs. ..
  39. Thompson B, Jin Y, Wu K, Colvin R, Luster A, Birnbaumer L, et al. Inhibition of G alpha i2 activation by G alpha i3 in CXCR3-mediated signaling. J Biol Chem. 2007;282:9547-55 pubmed
    ..This interplay has heretofore been masked by the use of pertussis toxin, a broad inhibitor of the G alpha(i/o) protein family. ..
  40. Berger H, Heinrich N, Wietfeld D, Bienert M, Beyermann M. Evidence that corticotropin-releasing factor receptor type 1 couples to Gs- and Gi-proteins through different conformations of its J-domain. Br J Pharmacol. 2006;149:942-7 pubmed
    ..It is further concluded that the allosteric mechanism of non-peptide antagonism is not valid for the Gs-mediated physiological activities of CRF(1). ..
  41. Kapoor N, Menon S, Chauhan R, Sachdev P, Sakmar T. Structural evidence for a sequential release mechanism for activation of heterotrimeric G proteins. J Mol Biol. 2009;393:882-97 pubmed publisher
    ..Interestingly, this mechanistic model for heterotrimeric G protein activation is similar to that suggested for the activation of the plant small G protein Rop4 by RopGEF8. ..
  42. Leduc M, Breton B, Gales C, Le Gouill C, Bouvier M, Chemtob S, et al. Functional selectivity of natural and synthetic prostaglandin EP4 receptor ligands. J Pharmacol Exp Ther. 2009;331:297-307 pubmed publisher
    ..The BRET-based methodology used for this first systematic assessment of a set of EP(4) agonists should be applicable for the study of other GPCRs. ..
  43. Wang J, Sengupta P, Guo Y, Golebiewska U, Scarlata S. Evidence for a second, high affinity Gbetagamma binding site on Galphai1(GDP) subunits. J Biol Chem. 2009;284:16906-13 pubmed publisher
    ..We propose that this second binding site serves to promote and stabilize G protein subunit interactions in the presence of competing cellular proteins. ..
  44. Reséndiz J, Kroll M, Lassila R. Protease-activated receptor-induced Akt activation--regulation and possible function. J Thromb Haemost. 2007;5:2484-93 pubmed
    ..Activated Akt regulates platelet function by modulating secretion and alpha(IIb)beta(3) activation. ..
  45. Harris J, Govindan J, Yamamoto I, Schwartz J, Kaverina I, Greenstein D. Major sperm protein signaling promotes oocyte microtubule reorganization prior to fertilization in Caenorhabditis elegans. Dev Biol. 2006;299:105-21 pubmed
    ..We propose that MSP-dependent microtubule reorganization promotes meiotic spindle assembly by facilitating the search and capture of microtubules by meiotic chromatin following NEBD. ..
  46. Castillo C, Albasanz J, Fernandez M, Martín M. Endogenous expression of adenosine A1, A2 and A3 receptors in rat C6 glioma cells. Neurochem Res. 2007;32:1056-70 pubmed
  47. Tsui D, van der Kooy D. Serotonin mediates a learned increase in attraction to high concentrations of benzaldehyde in aged C. elegans. Learn Mem. 2008;15:844-55 pubmed publisher
    ..We propose that associative learning may selectively modify pathways at or downstream from a low-affinity olfactory receptor. ..
  48. Zhao N, Wang H, Dow Edwards D. Cocaine exposure during the early postnatal period diminishes medial frontal cortex Gs coupling to dopamine D1-like receptors in adult rat. Neurosci Lett. 2008;438:159-62 pubmed publisher
  49. Lee M, Choi S, Hallden G, Yo S, Schichnes D, Aponte G. P2Y5 is a G(alpha)i, G(alpha)12/13 G protein-coupled receptor activated by lysophosphatidic acid that reduces intestinal cell adhesion. Am J Physiol Gastrointest Liver Physiol. 2009;297:G641-54 pubmed publisher
    ..This study elucidates a mechanism whereby LPA can act as a luminal and/or serosal cue to alter mucosal integrity. ..
  50. Vural A, Oner S, An N, Simon V, Ma D, Blumer J, et al. Distribution of activator of G-protein signaling 3 within the aggresomal pathway: role of specific residues in the tetratricopeptide repeat domain and differential regulation by the AGS3 binding partners Gi(alpha) and mammalian inscuteable. Mol Cell Biol. 2010;30:1528-40 pubmed publisher
    ..These data present AGS3, G-proteins, and mInsc as candidate proteins involved in regulating cellular stress associated with protein-processing pathologies. ..
  51. Bowers M, Hopf F, Chou J, Guillory A, Chang S, Janak P, et al. Nucleus accumbens AGS3 expression drives ethanol seeking through G betagamma. Proc Natl Acad Sci U S A. 2008;105:12533-8 pubmed publisher
    ..AGS3 up-regulation during abstinence may be a key determinant of the transition from social consumption to compulsion-like seeking during relapse. ..
  52. Tsai R, Tai Y, Tzeng J, Cherng C, Yeh C, Wong C. Ultra-low dose naloxone restores the antinociceptive effect of morphine in pertussis toxin-treated rats by reversing the coupling of mu-opioid receptors from Gs-protein to coupling to Gi-protein. Neuroscience. 2009;164:435-43 pubmed publisher
    ..We suggest that ultra-low dose naloxone might be clinically valuable in pain management. ..
  53. Bikkavilli R, Feigin M, Malbon C. G alpha o mediates WNT-JNK signaling through dishevelled 1 and 3, RhoA family members, and MEKK 1 and 4 in mammalian cells. J Cell Sci. 2008;121:234-45 pubmed publisher
    ..These data reveal both common and unique signaling elements in WNT3a-sensitive pathways, highlighting crosstalk from WNT3a-JNK to WNT3a-beta-catenin signaling. ..