Gene Symbol: Rgs4
Description: regulator of G-protein signaling 4
Alias: AA004315, AA597169, ESTM48, ESTM50, regulator of G-protein signaling 4
Species: mouse
Products:     Rgs4

Top Publications

  1. Grillet N, Dubreuil V, Dufour H, Brunet J. Dynamic expression of RGS4 in the developing nervous system and regulation by the neural type-specific transcription factor Phox2b. J Neurosci. 2003;23:10613-21 pubmed
    Previous studies have shown that members of the family of regulators of G-protein signaling (RGS), including RGS4, have a discrete expression pattern in the adult brain (Gold et al., 1997)...
  2. Grillet N, Pattyn A, Contet C, Kieffer B, Goridis C, Brunet J. Generation and characterization of Rgs4 mutant mice. Mol Cell Biol. 2005;25:4221-8 pubmed
    ..However, those have just begun to be explored in vivo. Here, we describe a mouse line deficient for Rgs4, a gene normally expressed early on in discrete populations of differentiating neurons and later on at multiple ..
  3. Caqueret A, Boucher F, Michaud J. Laminar organization of the early developing anterior hypothalamus. Dev Biol. 2006;298:95-106 pubmed
    ..We examined the expression pattern of 10 of the identified genes--Cart, Cbln1, Alcam, Unc-13c, Rgs4, Lnx4, Irx3, Sax1, Ldb2 and Neurod6--by in situ hybridization in E12.5 embryos...
  4. Albig A, Schiemann W. Identification and characterization of regulator of G protein signaling 4 (RGS4) as a novel inhibitor of tubulogenesis: RGS4 inhibits mitogen-activated protein kinases and vascular endothelial growth factor signaling. Mol Biol Cell. 2005;16:609-25 pubmed
    ..microarray analysis to further our understanding of tubulogenesis and observed a robust induction of regulator of G protein signaling 4 (RGS4) mRNA expression solely in tubulating cells, thereby implicating RGS4 as a potential regulator ..
  5. Chen Y, Liu Y, Cottingham C, McMahon L, Jiao K, Greengard P, et al. Neurabin scaffolding of adenosine receptor and RGS4 regulates anti-seizure effect of endogenous adenosine. J Neurosci. 2012;32:2683-95 pubmed publisher
    ..A(1) receptor (A1R) signaling by assembling a complex between the A1R and the regulator of G-protein signaling 4 (RGS4), a protein known to turn off G-protein signaling...
  6. Siedlecki A, Jin X, Thomas W, Hruska K, Muslin A. RGS4, a GTPase activator, improves renal function in ischemia-reperfusion injury. Kidney Int. 2011;80:263-71 pubmed publisher
    ..b>RGS4 is expressed in vascular smooth muscle cells in the kidney; however, its protein levels are low in many tissues due ..
  7. Hoekstra E, von Oerthel L, van der Linden A, Schellevis R, Scheppink G, Holstege F, et al. Lmx1a is an activator of Rgs4 and Grb10 and is responsible for the correct specification of rostral and medial mdDA neurons. Eur J Neurosci. 2013;37:23-32 pubmed publisher
    ..analysis in Lmx1a mouse mutant (dr/dr) embryos demonstrated a clear decrease in expression of the genes Grb10 and Rgs4, in and adjacent to the rostral and dorsal mdDA neuronal field and within the Lmx1a expression domain...
  8. Harris I, Treskov I, Rowley M, Heximer S, Kaltenbronn K, Finck B, et al. G-protein signaling participates in the development of diabetic cardiomyopathy. Diabetes. 2004;53:3082-90 pubmed
    ..mice with transgenic mice with cardiac-specific overexpression of regulator of G-protein signaling subtype 4 (RGS4), a GTPase activating protein for Gq and Gi...
  9. Eng S, Dykes I, Lanier J, Fedtsova N, Turner E. POU-domain factor Brn3a regulates both distinct and common programs of gene expression in the spinal and trigeminal sensory ganglia. Neural Dev. 2007;2:3 pubmed

More Information


  1. Stratinaki M, Varidaki A, Mitsi V, Ghose S, Magida J, Dias C, et al. Regulator of G protein signaling 4 [corrected] is a crucial modulator of antidepressant drug action in depression and neuropathic pain models. Proc Natl Acad Sci U S A. 2013;110:8254-9 pubmed publisher
    b>Regulator of G protein signaling 4 (Rgs4) is a signal transduction protein that controls the function of monoamine, opiate, muscarinic, and other G protein-coupled receptors via interactions with G? subunits...
  2. de Vries L, Gist Farquhar M. RGS proteins: more than just GAPs for heterotrimeric G proteins. Trends Cell Biol. 1999;9:138-44 pubmed
    ..This review summarizes recent findings on RGS proteins, especially those that implicate RGS proteins in more than just enhancing the GTPase activity of their Galpha subunit targets. ..
  3. Ruiz de Azua I, Nakajima K, Rossi M, Cui Y, Jou W, Gavrilova O, et al. Spinophilin as a novel regulator of M3 muscarinic receptor-mediated insulin release in vitro and in vivo. FASEB J. 2012;26:4275-86 pubmed publisher
    ..resonance energy transfer technology, suggested that SPL is able to recruit regulator of G-protein signaling 4 (RGS4) to the M3R signaling complex in an agonist-dependent fashion...
  4. Jaba I, Zhuang Z, Li N, Jiang Y, Martin K, Sinusas A, et al. NO triggers RGS4 degradation to coordinate angiogenesis and cardiomyocyte growth. J Clin Invest. 2013;123:1718-31 pubmed
    ..induced myocardial hypertrophy by promoting proteasomal degradation of regulator of G protein signaling type 4 (RGS4), thus relieving the repression of the G??/PI3K?/AKT/mTORC1 pathway that stimulates cardiomyocyte growth...
  5. Ebert P, Campbell D, Levitt P. Bacterial artificial chromosome transgenic analysis of dynamic expression patterns of regulator of G-protein signaling 4 during development. I. Cerebral cortex. Neuroscience. 2006;142:1145-61 pubmed
    ..to create transgenic mice that express GFP under the control of endogenous regulator of G-protein signaling 4 (RGS4) enhancer elements. This report focuses on expression patterns in the developing and mature cerebral cortex...
  6. Ding L, Mychaleckyj J, Hegde A. Full length cloning and expression analysis of splice variants of regulator of G-protein signaling RGS4 in human and murine brain. Gene. 2007;401:46-60 pubmed
    RGS4 (regulator of G protein signaling 4) protein is a GTPase-activating protein specific for Gi/o and Gq alpha subunits. It is highly expressed in brain but the mechanisms by which RGS4 expression is regulated remain unknown...
  7. Wydeven N, Posokhova E, Xia Z, Martemyanov K, Wickman K. RGS6, but not RGS4, is the dominant regulator of G protein signaling (RGS) modulator of the parasympathetic regulation of mouse heart rate. J Biol Chem. 2014;289:2440-9 pubmed publisher
    ..Both RGS4 and RGS6-G?5 have been implicated in these processes...
  8. Harder S, Lu X, Wang W, Buck F, Gershengorn M, Bruhn T. Regulator of G protein signaling 4 suppresses basal and thyrotropin releasing-hormone (TRH)-stimulated signaling by two mouse TRH receptors, TRH-R(1) and TRH-R(2). Endocrinology. 2001;142:1188-94 pubmed
    ..We found that regulator of G protein signaling 4 (RGS4), which differentially inhibits signaling by other receptors that couple to Gq, inhibits TRH-..
  9. Han M, Renthal W, Ring R, Rahman Z, Psifogeorgou K, Howland D, et al. Brain region specific actions of regulator of G protein signaling 4 oppose morphine reward and dependence but promote analgesia. Biol Psychiatry. 2010;67:761-9 pubmed publisher
    b>Regulator of G protein signaling 4 (RGS4) is one of the smaller members of the RGS family of proteins, which are known to control signaling amplitude and duration via interactions with G protein alpha subunits or other signaling molecules...
  10. Kvajo M, McKellar H, Gogos J. Avoiding mouse traps in schizophrenia genetics: lessons and promises from current and emerging mouse models. Neuroscience. 2012;211:136-64 pubmed publisher
    ..Finally, we discuss emerging mouse models, such as second-generation pathophysiology models based on innovative approaches that are facilitated by the information gathered from the current genetic mouse models. ..
  11. Tokudome T, Kishimoto I, Horio T, Arai Y, Schwenke D, Hino J, et al. Regulator of G-protein signaling subtype 4 mediates antihypertrophic effect of locally secreted natriuretic peptides in the heart. Circulation. 2008;117:2329-39 pubmed publisher
    ..In the present report, we examined the role of regulator of G-protein signaling subtype 4 (RGS4), a GTPase activating protein for G(q) and G(i), in the antihypertrophic effects of GC-A...
  12. Kim H, Ryu J, Woo H, Cho S, Sung M, Kim S, et al. Patterns of gene expression associated with Pten deficiency in the developing inner ear. PLoS ONE. 2014;9:e97544 pubmed publisher
    ..e., secreted phosphoprotein 1 (Spp1)-mediated cellular movement and regulator of G-protein signaling 4 (Rgs4)-mediated axon guidance). This result was consistent with the phenotypic defects of SGNs in Pten cKO mice (e.g...
  13. Madigan L, Wong G, Gordon E, Chen W, Balenga N, Koziol White C, et al. RGS4 Overexpression in Lung Attenuates Airway Hyperresponsiveness in Mice. Am J Respir Cell Mol Biol. 2018;58:89-98 pubmed publisher
    ..RGS2- and RGS5-deficient mice develop AHR spontaneously. Although RGS4 is upregulated in ASM from patients with severe asthma, the effects of increased RGS4 expression on AHR in vivo are ..
  14. Chen C, Wieland T, Simon M. RGS-r, a retinal specific RGS protein, binds an intermediate conformation of transducin and enhances recycling. Proc Natl Acad Sci U S A. 1996;93:12885-9 pubmed
    ..This specific interaction further rationalizes the kinetics of the phototransduction cascade and provides a general hypothesis to explain the mechanism of interaction of RGS proteins with other G proteins. ..
  15. Opel A, Nobles M, Montaigne D, Finlay M, Anderson N, Breckenridge R, et al. Absence of the Regulator of G-protein Signaling, RGS4, Predisposes to Atrial Fibrillation and Is Associated with Abnormal Calcium Handling. J Biol Chem. 2015;290:19233-44 pubmed publisher
    ..We address whether the attenuation of RGS4 function may promote AF and the mechanism through which this occurs...
  16. Song K, Kim H, Kim K, Lee J, Yoon J. Regulator of G-protein signaling 4 suppresses LPS-induced MUC5AC overproduction in the airway. Am J Respir Cell Mol Biol. 2009;41:40-9 pubmed publisher
    ..These results give additional insights into the molecular mechanism of negative regulation of mucin overproduction and enhance our understanding of mucus hypersecretion during airway mucosal inflammation. ..
  17. Inoue K, Hirose M, Inoue H, Hatanaka Y, Honda A, Hasegawa A, et al. The Rodent-Specific MicroRNA Cluster within the Sfmbt2 Gene Is Imprinted and Essential for Placental Development. Cell Rep. 2017;19:949-956 pubmed publisher
    ..Our study has provided experimental evidence for the indispensable roles of placental miRNAs in trophoblast proliferation and thus fetal development. ..
  18. Wang Q, Liu Chen L, Traynor J. Differential modulation of mu- and delta-opioid receptor agonists by endogenous RGS4 protein in SH-SY5Y cells. J Biol Chem. 2009;284:18357-67 pubmed publisher
    ..A variety of RGS proteins have been reported to modulate opioid receptor signaling. Here we show that RGS4 is abundantly expressed in human neuroblastoma SH-SY5Y cells that endogenously express mu- and delta-opioid ..
  19. Serafimidis I, Heximer S, Beis D, Gavalas A. G protein-coupled receptor signaling and sphingosine-1-phosphate play a phylogenetically conserved role in endocrine pancreas morphogenesis. Mol Cell Biol. 2011;31:4442-53 pubmed publisher
    ..b>Rgs4, a dedicated regulator of GPCR signaling, was specifically expressed in early epithelial endocrine progenitors of ..
  20. Nomoto S, Adachi K, Yang L, Hirata Y, Muraguchi S, Kiuchi K. Distribution of RGS4 mRNA in mouse brain shown by in situ hybridization. Biochem Biophys Res Commun. 1997;241:281-7 pubmed
    ..Some, including RGS4, have been shown to act as GTPase-activating proteins for several members of the Gi alpha subunits and the Gq alpha ..
  21. Ruiz de Azua I, Scarselli M, Rosemond E, Gautam D, Jou W, Gavrilova O, et al. RGS4 is a negative regulator of insulin release from pancreatic beta-cells in vitro and in vivo. Proc Natl Acad Sci U S A. 2010;107:7999-8004 pubmed publisher
    ..To address this issue, we initially demonstrated that MIN6 insulinoma cells express functional M3Rs and that RGS4 was by far the most abundant RGS protein expressed by these cells...
  22. Ho A, Mackay R, Dodd P, Lewohl J. Association of polymorphisms in RGS4 and expression of RGS transcripts in the brains of human alcoholics. Brain Res. 2010;1340:1-9 pubmed publisher
    ..We used Real Time PCR to measure the expression of two members of the RGS family, RGS4 and RGS7, in the superior frontal gyrus and primary motor cortex from alcoholic and non-alcoholic cases...
  23. Siedlecki A, Anderson J, Jin X, Garbow J, Lupu T, Muslin A. RGS4 controls renal blood flow and inhibits cyclosporine-mediated nephrotoxicity. Am J Transplant. 2010;10:231-41 pubmed publisher
    ..b>RGS4 is a GTPase activating protein that promotes the deactivation of Gq and Gi family members...
  24. Pang P, Jin X, Proctor B, Farley M, Roy N, Chin M, et al. RGS4 inhibits angiotensin II signaling and macrophage localization during renal reperfusion injury independent of vasospasm. Kidney Int. 2015;87:771-83 pubmed publisher
    ..reperfusion injury we studied the potential anti-inflammatory role of the Gα-related RGS protein, RGS4. Transgenic RGS4 mice were resistant to 25 min injury, although post-ischemic renal arteriolar diameter was ..
  25. Iankova I, Chavey C, Clapé C, Colomer C, Guerineau N, Grillet N, et al. Regulator of G protein signaling-4 controls fatty acid and glucose homeostasis. Endocrinology. 2008;149:5706-12 pubmed publisher
    ..Consequently, RGS4-/- mice have increased concentration of circulating free fatty acids; abnormally accumulate fatty acids in liver, ..
  26. Jung S, Son H, Lee D, Roh G, Kang S, Cho G, et al. Decreased levels of RGS4 in the paraventricular nucleus facilitate GABAergic inhibition during the acute stress response. Biochem Biophys Res Commun. 2016;472:276-80 pubmed publisher
    ..We previously showed that regulators of G-protein signaling 4 (RGS4), which decreases in the paraventricular nucleus (PVN) during acute stress, forms a complex with the GABAB receptor...
  27. Pacey L, Doss L, Cifelli C, van der Kooy D, Heximer S, Hampson D. Genetic deletion of regulator of G-protein signaling 4 (RGS4) rescues a subset of fragile X related phenotypes in the FMR1 knockout mouse. Mol Cell Neurosci. 2011;46:563-72 pubmed publisher
    ..Notably, RGS4 is highly expressed in brain and has been shown to negatively regulate signaling through Group I mGluRs and GABA(B) ..
  28. McOmish C, Burrows E, Howard M, Hannan A. PLC-beta1 knockout mice as a model of disrupted cortical development and plasticity: behavioral endophenotypes and dysregulation of RGS4 gene expression. Hippocampus. 2008;18:824-34 pubmed publisher
    ..These signaling pathways, furthermore, are susceptible to modulation by RGS4, one of the more promising candidate genes for schizophrenia...
  29. Teplyuk N, Galindo M, Teplyuk V, Pratap J, Young D, Lapointe D, et al. Runx2 regulates G protein-coupled signaling pathways to control growth of osteoblast progenitors. J Biol Chem. 2008;283:27585-97 pubmed publisher
    ..g. Rgs2, Rgs4, Rgs5, Rgs16, Gpr23, Gpr30, Gpr54, Gpr64, and Gna13)...
  30. Cheng T, Gong Q. Secreted TARSH regulates olfactory mitral cell dendritic complexity. Eur J Neurosci. 2009;29:1083-95 pubmed publisher
    ..Dendritic morphological changes were also observed in mitral cells overexpressing TARSH themselves. We propose that TARSH is part of the genetic program that regulates mitral cell dendritic refinement. ..
  31. Cifelli C, Rose R, Zhang H, Voigtlaender Bolz J, Bolz S, Backx P, et al. RGS4 regulates parasympathetic signaling and heart rate control in the sinoatrial node. Circ Res. 2008;103:527-35 pubmed publisher
    ..Our results demonstrate that RGS4 mRNA levels are higher in the SAN compared to right atrium...
  32. Ha S, Stottmann R, Furley A, Beier D. A forward genetic screen in mice identifies mutants with abnormal cortical patterning. Cereb Cortex. 2015;25:167-79 pubmed publisher
    ..ENU) mutagenesis was performed using mice expressing LacZ reporter genes in layers II/III and V of the cortex (Rgs4-lacZ) or in corticofugal axons (TAG1-tau-lacZ). Four lines with abnormal cortical lamination have been identified...
  33. Lee M, Tasaki T, Moroi K, An J, Kimura S, Davydov I, et al. RGS4 and RGS5 are in vivo substrates of the N-end rule pathway. Proc Natl Acad Sci U S A. 2005;102:15030-5 pubmed
    ..Here, we report that the ATE1 Arg-transferase mediates the in vivo degradation of RGS4 and RGS5, which are negative regulators of specific G proteins whose functions include cardiac growth and ..
  34. Osterberg N, Wiehle M, Oehlke O, Heidrich S, Xu C, Fan C, et al. Sim1 is a novel regulator in the differentiation of mouse dorsal raphe serotonergic neurons. PLoS ONE. 2011;6:e19239 pubmed publisher
    ..Moreover, the transcription factor Lhx8 and the modulator of 5-HT(1A)-mediated neurotransmitter release, Rgs4, exhibit significant higher expression in ventral hindbrain, compared to midbrain and are target genes of Sim1...
  35. Pallaki P, Georganta E, Serafimidis I, Papakonstantinou M, Papanikolaou V, Koutloglou S, et al. A novel regulatory role of RGS4 in STAT5B activation, neurite outgrowth and neuronal differentiation. Neuropharmacology. 2017;117:408-421 pubmed publisher
    The Regulator of G protein Signalling 4 (RGS4) is a multitask protein that interacts with and negatively modulates opioid receptor signalling...
  36. Song K, Choi Y, Kim J, Lee H, Lee T, Yoon J. Suppression of prostaglandin E2-induced MUC5AC overproduction by RGS4 in the airway. Am J Physiol Lung Cell Mol Physiol. 2009;296:L684-92 pubmed publisher
    ..with wild-type mice at both transcriptional and translational levels, and it was dramatically suppressed in Rgs4 KO mice that had been infected with lentivirus expressing RGS4 (lenti::RGS4) compared with lentivirus expressing ..
  37. Chambers D, Wilson L, Alfonsi F, Hunter E, Saxena U, Blanc E, et al. Rhombomere-specific analysis reveals the repertoire of genetic cues expressed across the developing hindbrain. Neural Dev. 2009;4:6 pubmed publisher
    ..These findings give the first genome-wide insight into the complexity of gene expression during patterning of the developing hindbrain. ..
  38. Winden K, Oldham M, Mirnics K, Ebert P, Swan C, Levitt P, et al. The organization of the transcriptional network in specific neuronal classes. Mol Syst Biol. 2009;5:291 pubmed publisher
    ..Finally, we show that galectin-1 is a new interneuron marker, and we validate network predictions in vivo using Rgs4 and Dlx1/2 knockout mice...
  39. Yoon S, Woo J, Park J, Choi E, Shin H, Roh D, et al. Intrathecal RGS4 inhibitor, CCG50014, reduces nociceptive responses and enhances opioid-mediated analgesic effects in the mouse formalin test. Anesth Analg. 2015;120:671-7 pubmed publisher
    The regulator of G-protein signaling protein type 4 (RGS4) accelerates the guanosine triphosphatase activity of G(αi) and G(αo), resulting in the inactivation of G-protein-coupled receptor signaling...
  40. Nagata Y, Oda M, Nakata H, Shozaki Y, Kozasa T, Todokoro K. A novel regulator of G-protein signaling bearing GAP activity for Galphai and Galphaq in megakaryocytes. Blood. 2001;97:3051-60 pubmed
    ..Thus, RGS18 may play an important role in proliferation, differentiation, and/or migration of megakaryocytes. ..
  41. Bilger A, Bennett L, Carabeo R, Chiaverotti T, Dvorak C, Liss K, et al. A potent modifier of liver cancer risk on distal mouse chromosome 1: linkage analysis and characterization of congenic lines. Genetics. 2004;167:859-66 pubmed
    ..Thus, distal chromosome 1 carries one or more genes that are sufficient to confer susceptibility to liver cancer. ..