Gene Symbol: Gnai2
Description: G protein subunit alpha i2
Alias: Galphai2, guanine nucleotide-binding protein G(i) subunit alpha-2, G alpha inhibitory type 2 (a), G alpha inhibitory type 2 (b), GTP-binding protein (G-alpha-i2), adenylate cyclase-inhibiting G alpha protein, guanine nucleotide binding protein (G protein), alpha inhibiting 2, guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 2, guanine nucleotide binding protein, alpha inhibiting 2, guanine nucleotide-binding protein G(i), alpha-2 subunit
Species: rat
Products:     Gnai2

Top Publications

  1. 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. ..
  2. Jones D, Reed R. Molecular cloning of five GTP-binding protein cDNA species from rat olfactory neuroepithelium. J Biol Chem. 1987;262:14241-9 pubmed
    ..In olfactory tissue, G alpha s was the most abundant of these messages and in combination with the biochemical studies suggests that G alpha s is the G-protein component of the olfactory signal transduction cascade. ..
  3. Shinohara H, Udagawa J, Morishita R, Ueda H, Otani H, Semba R, et al. Gi2 signaling enhances proliferation of neural progenitor cells in the developing brain. J Biol Chem. 2004;279:41141-8 pubmed
    ..These findings indicate that Gi2 mediates signaling from receptors such as the endothelin-B receptor to maintain mitogenic activity in the neural progenitor cells of developing brain. ..
  4. Rudolph U, Spicher K, Birnbaumer L. Adenylyl cyclase inhibition and altered G protein subunit expression and ADP-ribosylation patterns in tissues and cells from Gi2 alpha-/-mice. Proc Natl Acad Sci U S A. 1996;93:3209-14 pubmed
  5. Chen F, Spicher K, Jiang M, Birnbaumer L, Wetzel G. Lack of muscarinic regulation of Ca(2+) channels in G(i2)alpha gene knockout mouse hearts. Am J Physiol Heart Circ Physiol. 2001;280:H1989-95 pubmed
    ..Further studies are needed to delineate the possible interaction of G(i) and other cell signaling proteins and to clarify the level of interaction of G protein-coupled regulation of L-type Ca(2+) current in the heart...
  6. Dezaki K, Kakei M, Yada T. Ghrelin uses Galphai2 and activates voltage-dependent K+ channels to attenuate glucose-induced Ca2+ signaling and insulin release in islet beta-cells: novel signal transduction of ghrelin. Diabetes. 2007;56:2319-27 pubmed
  7. Möller D, Kling R, Skultety M, Leuner K, Hubner H, Gmeiner P. Functionally selective dopamine D?, D? receptor partial agonists. J Med Chem. 2014;57:4861-75 pubmed publisher
    ..Ligand efficacy and selectivity between D(2S) and D3 activation were strongly influenced by regiochemistry and the nature of functional groups attached to the pyrazolo[1,5-a]pyridine moiety. ..
  8. Wang X, Yang X, Lu L, Zhang L, Sun Y, Wang J, et al. [Alteration of the expression of rat cardiac Galphaq/11 and Gialpha2 proteins during endothelin-1 pre-treatment]. Sheng Li Xue Bao. 2000;52:459-62 pubmed
    ..0% (P<0.01) in ET-1 group. In conclusion, activation of G alphaq/11 may be related to the protecting mechanism of ET-1 pre-treatment and IP, whereas Gialpha2 may only play a role in ET-1 pre-treatment. ..
  9. Rucha A, Verspohl E. Heterologous desensitization of insulin secretion by GIP (glucose-dependent insulinotropic peptide) in INS-1 cells: the significance of Galphai2 and investigations on the mechanism involved. Cell Biochem Funct. 2005;23:205-12 pubmed
    ..This was accompanied by similar changes in Galphai2 mRNA...

More Information


  1. Schuller U, Lamp E, Schilling K. Developmental expression of heterotrimeric G-proteins in the murine cerebellar cortex. Histochem Cell Biol. 2001;116:149-59 pubmed
  2. DeGeorge B, Gao E, Boucher M, Vinge L, Martini J, Raake P, et al. Targeted inhibition of cardiomyocyte Gi signaling enhances susceptibility to apoptotic cell death in response to ischemic stress. Circulation. 2008;117:1378-87 pubmed publisher
    ..Our results with GiCT indicate that upregulation of G alpha(i2) is an adaptive protective response after ischemia to shield myocytes from apoptosis. ..
  3. El Andalousi J, Li Y, Anand Srivastava M. Natriuretic peptide receptor-C agonist attenuates the expression of cell cycle proteins and proliferation of vascular smooth muscle cells from spontaneously hypertensive rats: role of Gi proteins and MAPkinase/PI3kinase signaling. PLoS ONE. 2013;8:e76183 pubmed publisher
    ..It may be suggested that C-ANP4-23 could be used as a therapeutic agent in the treatment of vascular complications associated with hypertension, atherosclerosis and restenosis. ..
  4. Linder M, Ewald D, Miller R, Gilman A. Purification and characterization of Go alpha and three types of Gi alpha after expression in Escherichia coli. J Biol Chem. 1990;265:8243-51 pubmed
    ..These results are consistent with the hypothesis that G protein beta gamma subunits are primarily responsible for inhibition of adenylyl cyclase activity. ..
  5. Wang Y, Wu L, Ge M. [Alterations of cardiac Gi protein alpha subunits during ischemia-reperfusion in rats]. Sheng Li Xue Bao. 1998;50:514-8 pubmed
    ..The results suggested that the increased expression of cardiac Gi may contribute to the dysfunction of adenyl cyclase signal transduction system and the impaired cardiac function during ischemia-reperfusion. ..
  6. Li Y, Descorbeth M, Anand Srivastava M. Role of oxidative stress in high glucose-induced decreased expression of Gialpha proteins and adenylyl cyclase signaling in vascular smooth muscle cells. Am J Physiol Heart Circ Physiol. 2008;294:H2845-54 pubmed publisher
    ..These results suggest that high glucose-induced decreased levels of Gialpha proteins and associated signaling in A10 VSMCs may be attributed to the enhanced oxidative stress due to augmented levels of peroxynitrite and not to H2O2. ..
  7. Melien O, Christoffersen T, Sioud M. Evidence for the involvement of Gi2 in activation of extracellular signal-regulated kinases in hepatocytes. BMC Cell Biol. 2001;2:13 pubmed
    ..The present data suggest an important role of Gi2 in PGF2alpha -induced ERK1/2 signaling in hepatocytes. ..
  8. 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. ..
  9. Baculikova M, Fiala R, Jezova D, Macho L, Zorad S. Rats with monosodium glutamate-induced obesity and insulin resistance exhibit low expression of Galpha(i2) G-protein. Gen Physiol Biophys. 2008;27:222-6 pubmed
  10. Mönkkönen K, Hakumäki J, Hirst R, Miettinen R, O Callaghan C, Mannisto P, et al. Intracerebroventricular antisense knockdown of G alpha i2 results in ciliary stasis and ventricular dilatation in the rat. BMC Neurosci. 2007;8:26 pubmed
    In the CNS, the heterotrimeric G protein Galphai2 is a minor Galpha subunit with restricted localization in the ventricular regions including the ependymal cilia...
  11. Zhong M, Clarke S, Vo B, Khan S. The essential role of Gi?2 in prostate cancer cell migration. Mol Cancer Res. 2012;10:1380-8 pubmed publisher
    ..In conclusion, Gi?2 plays an essential role in OXT and EGF signaling to induce prostate cancer cell migration. ..
  12. Tall G, Krumins A, Gilman A. Mammalian Ric-8A (synembryn) is a heterotrimeric Galpha protein guanine nucleotide exchange factor. J Biol Chem. 2003;278:8356-62 pubmed
    ..Ric-8A interacts with GDP-bound Galpha proteins, stimulates release of GDP, and forms a stable nucleotide-free transition state complex with the Galpha protein; this complex dissociates upon binding of GTP to Galpha. ..
  13. Head B, Patel H, Roth D, Lai N, Niesman I, Farquhar M, et al. G-protein-coupled receptor signaling components localize in both sarcolemmal and intracellular caveolin-3-associated microdomains in adult cardiac myocytes. J Biol Chem. 2005;280:31036-44 pubmed
  14. Cioffi J, Wackym P, Erbe C, Gaggl W, Popper P. Molecular characterization of two novel splice variants of G alphai2 in the rat vestibular periphery. Brain Res Mol Brain Res. 2005;137:89-97 pubmed
    ..a partial sequence, termed Galphai2vest, obtained from rat vestibular tissue that was nearly identical to rat Galphai2. Using an experimental strategy to further characterize Galphai2vest (GenBank accession number AF189020) and ..
  15. Sarkar O, Li Y, Anand Srivastava M. Nitric oxide attenuates overexpression of Gi? proteins in vascular smooth muscle cells from SHR: Role of ROS and ROS-mediated signaling. PLoS ONE. 2017;12:e0179301 pubmed publisher
  16. Hashim S, Anand Srivastava M. Losartan-induced attenuation of blood pressure in L-NAME hypertensive rats is associated with reversal of the enhanced expression of Gi alpha proteins. J Hypertens. 2004;22:181-90 pubmed
    ..These results suggest the implication of AT1 receptors in enhanced expression of Gi alpha proteins and increased blood pressure in L-NAME-induced hypertension. ..
  17. de Vries L, Fischer T, Tronchere H, Brothers G, Strockbine B, Siderovski D, et al. Activator of G protein signaling 3 is a guanine dissociation inhibitor for Galpha i subunits. Proc Natl Acad Sci U S A. 2000;97:14364-9 pubmed
    ..Inhibition of the Galpha subunit and stimulation of heterotrimeric G protein signaling, presumably by stimulating Gbetagamma, extend the possibilities for modulating signal transduction through heterotrimeric G proteins. ..
  18. Nakagawa H, Umadome H, Miyazaki S, Tanaka K, Nishimura K, Komori M, et al. ER-resident Gi2 protein controls sar1 translocation onto the ER during budding of transport vesicles. J Cell Biochem. 2011;112:2250-6 pubmed publisher
  19. Jeong S, Ikeda S. Effect of G protein heterotrimer composition on coupling of neurotransmitter receptors to N-type Ca(2+) channel modulation in sympathetic neurons. Proc Natl Acad Sci U S A. 2000;97:907-12 pubmed
    ..Thus, if exquisite Galphabetagamma-coupling specificity exists in situ, it cannot arise solely from the inherent inability of other Galphabetagamma combinations to form functional signaling complexes. ..
  20. Kimple R, de Vries L, Tronchere H, Behe C, Morris R, Gist Farquhar M, et al. RGS12 and RGS14 GoLoco motifs are G alpha(i) interaction sites with guanine nucleotide dissociation inhibitor Activity. J Biol Chem. 2001;276:29275-81 pubmed
    ..The presence of two, independent G alpha interaction sites suggests that RGS12 and RGS14 participate in a complex coordination of G-protein signaling beyond simple G alpha GAP activity. ..
  21. Wang X, Fan X, Cai L, Liu S, Cong X, Chen X. Lysophosphatidic acid rescues bone mesenchymal stem cells from hydrogen peroxide-induced apoptosis. Apoptosis. 2015;20:273-84 pubmed publisher
  22. Berg K, Zardeneta G, Hargreaves K, Clarke W, Milam S. Integrins regulate opioid receptor signaling in trigeminal ganglion neurons. Neuroscience. 2007;144:889-97 pubmed
    ..g. Galphai vs. Galphas). Collectively, these data provide the first evidence that specific integrins regulate opioid receptor signaling in sensory neurons. ..
  23. Khan Z, Gutierrez A. Distribution of C-terminal splice variant of G alpha i2 in rat and monkey brain. Neuroscience. 2004;127:833-43 pubmed
    The significance of Galphai2 in neural signal transmission is well defined. However, the function of its alternative splice variant named sGi2 is unknown...
  24. Xia S, Hu C, Fang J, Di Y, Zhao Z, Liu L. G[alpha]i2 and G[alpha]q expression change in pancreatic tissues and BN52021 effects in rats with severe acute pancreatitis. Pancreas. 2008;37:170-5 pubmed publisher
    ..05). G[alpha]i2, G[alpha]q mRNA, and their proteins in SAP increase. BN52021 decreases G[alpha]i2 and G[alpha]q. ..
  25. Ceolotto G, Papparella I, Sticca A, Bova S, Cavalli M, Cargnelli G, et al. An abnormal gene expression of the beta-adrenergic system contributes to the pathogenesis of cardiomyopathy in cirrhotic rats. Hepatology. 2008;48:1913-23 pubmed publisher
    ..These results indicate that overexpression of Galpha(i2), PDE2a, and RGS2 down-regulates the beta-adrenergic signaling pathway, thus contributing to the pathogenesis of cirrhotic cardiomyopathy. ..
  26. Clement N, Glorian M, Raymondjean M, Andreani M, Limon I. PGE2 amplifies the effects of IL-1beta on vascular smooth muscle cell de-differentiation: a consequence of the versatility of PGE2 receptors 3 due to the emerging expression of adenylyl cyclase 8. J Cell Physiol. 2006;208:495-505 pubmed
    ..Using real time PCR, pharmacological tools and small interfering RNA (siRNA), we demonstrated that the different integration of PGE2 signals depends on the upregulation of calcium/calmodulin stimulable adenylyl cyclase 8. ..
  27. Padia S, Carey R. AT2 receptors: beneficial counter-regulatory role in cardiovascular and renal function. Pflugers Arch. 2013;465:99-110 pubmed publisher
  28. Ali El Basyuni Y, Li Y, Anand Srivastava M. Knockdown of Inhibitory Guanine Nucleotide Binding Protein Gi?-2 by Antisense Oligodeoxynucleotides Attenuates the Development of Hypertension and Tachycardia in Spontaneously Hypertensive Rats. J Am Heart Assoc. 2016;5: pubmed
    ..These results suggested that the enhanced expression of Gi?-2 but not Gi?-3 protein plays an important role in the pathogenesis of hypertension and tachycardia in SHRs. ..
  29. Sánchez Blázquez P, De Antonio I, Montero C, Garzón J. Exogenous myristoylated-G(i2)alpha subunits of GTP-binding proteins are mitogens following their internalization by astrocytes in culture. Brain Res Mol Brain Res. 2003;110:15-26 pubmed
    ..Thus, these proteins may have clinical applications for compensating deficits in the transduction mechanisms associated with several neurological diseases, or as a non-invasive membrane traversing carriers. ..
  30. Lerman B, Dong B, Stein K, Markowitz S, Linden J, Catanzaro D. Right ventricular outflow tract tachycardia due to a somatic cell mutation in G protein subunitalphai2. J Clin Invest. 1998;101:2862-8 pubmed
    ..Genomic sequences of the inhibitory G protein Galphai2 were determined after amplification by PCR and subcloning...
  31. Haga T. Molecular properties of muscarinic acetylcholine receptors. Proc Jpn Acad Ser B Phys Biol Sci. 2013;89:226-56 pubmed
    ..This paper summarizes the molecular properties of muscarinic receptors with reference to the historical background and bias to studies performed in our laboratories...
  32. Itoh H, Kozasa T, Nagata S, Nakamura S, Katada T, Ui M, et al. Molecular cloning and sequence determination of cDNAs for alpha subunits of the guanine nucleotide-binding proteins Gs, Gi, and Go from rat brain. Proc Natl Acad Sci U S A. 1986;83:3776-80 pubmed
    ..The Go alpha clone encoded a sequence of 310 amino acid residues that lacked the NH2 terminus. The homology of the alpha subunits of Gs, Gi, Go, transducin, and ras-encoded protein is discussed. ..
  33. López Aranda M, López Téllez J, Blanco E, Masmudi Martín M, Navarro Lobato I, Khan Z. A dynamic expression pattern of sGalpha(i2) protein during early period of postnatal rat brain development. Int J Dev Neurosci. 2008;26:611-24 pubmed publisher
  34. Tao J, Malbon C, Wang H. Galpha(i2) enhances insulin signaling via suppression of protein-tyrosine phosphatase 1B. J Biol Chem. 2001;276:39705-12 pubmed
    ..These data provide the first molecular basis for the interplay between Galpha(i2) and insulin signaling, i.e. activation of Galpha(i2) can suppress both the expression and activity of PTP1B in insulin-sensitive tissues. ..
  35. Straiker A, Borden C, Sullivan J. G-protein alpha subunit isoforms couple differentially to receptors that mediate presynaptic inhibition at rat hippocampal synapses. J Neurosci. 2002;22:2460-8 pubmed
    ..Differential coupling of G-protein alpha subunits may be a means of achieving specificity between different GPCRs and their molecular targets for mediating presynaptic inhibition. ..
  36. Kapusta D, Pascale C, Wainford R. Brain heterotrimeric G?i?-subunit protein-gated pathways mediate central sympathoinhibition to maintain fluid and electrolyte homeostasis during stress. FASEB J. 2012;26:2776-87 pubmed publisher
    ..Collectively, these data demonstrate that PVN G?i(2) protein pathways play an endogenous role in maintaining fluid and electrolyte balance by controlling the influence the sympathetic nervous system has on the renal handling of sodium. ..
  37. Jain M, Lim C, Nagata K, Davis V, Milstone D, Liao R, et al. Targeted inactivation of Galpha(i) does not alter cardiac function or beta-adrenergic sensitivity. Am J Physiol Heart Circ Physiol. 2001;280:H569-75 pubmed
    ..These data demonstrate no observable role for inhibitory G proteins in mediating basal cardiac function or sensitivity to beta-AR stimulation in nonpathological myocardium...
  38. Gromada J, Høy M, Buschard K, Salehi A, Rorsman P. Somatostatin inhibits exocytosis in rat pancreatic alpha-cells by G(i2)-dependent activation of calcineurin and depriming of secretory granules. J Physiol. 2001;535:519-32 pubmed
    ..We propose that somatostatin receptors associate with L-type Ca(2+) channels and couple to G(i2) proteins leading to a localised activation of calcineurin and depriming of secretory granules situated close to the L-type Ca(2+) channels. ..
  39. Rau T, Nose M, Remmers U, Weil J, Weissmüller A, Davia K, et al. Overexpression of wild-type Galpha(i)-2 suppresses beta-adrenergic signaling in cardiac myocytes. FASEB J. 2003;17:523-5 pubmed
    ..The data argue for an important, independent role of the Galpha(i)-2 increase in heart failure. ..