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regulator of G-protein signaling 4

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Target not currently curated in GtoImmuPdb

Target id: 2811

Nomenclature: regulator of G-protein signaling 4

Abbreviated Name: RGS4

Family: R4 family

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 205 1q23.3 RGS4 regulator of G protein signaling 4
Mouse - 205 1 76.84 cM Rgs4 regulator of G-protein signaling 4
Rat - 205 13q24 Rgs4 regulator of G-protein signaling 4
Previous and Unofficial Names Click here for help
ESTM48 | ESTM50
Database Links Click here for help
Alphafold P49798 (Hs), O08899 (Mm), P49799 (Rn)
CATH/Gene3D 1.10.196.10
ChEMBL Target CHEMBL1795091 (Hs)
Ensembl Gene ENSG00000117152 (Hs), ENSMUSG00000038530 (Mm), ENSRNOG00000002773 (Rn)
Entrez Gene 5999 (Hs), 19736 (Mm), 29480 (Rn)
Human Protein Atlas ENSG00000117152 (Hs)
KEGG Gene hsa:5999 (Hs), mmu:19736 (Mm), rno:29480 (Rn)
OMIM 602516 (Hs)
Pharos P49798 (Hs)
RefSeq Nucleotide NM_001102445 (Hs), NM_009062 (Mm), NM_017214 (Rn)
RefSeq Protein NP_001106851 (Hs), NP_001095915 (Hs), NP_033088 (Mm), NP_058910 (Rn)
UniProtKB P49798 (Hs), O08899 (Mm), P49799 (Rn)
Wikipedia RGS4 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  High-resolution solution structure of free RGS4 by NMR
PDB Id:  1EZY
Resolution:  0.0Å
Species:  Rat
References:  43
Associated Proteins Click here for help
G Proteins
Name References
Gz 21
Gαq/11 2,21
Gαs
Golf
Gαi/0 2-3,21
Gα12/13 7
Interacting Proteins
Name Effect References
GPCR-Kir3 channel complex Accelerated GIRK activation and deactivation 23
μ receptor Reduced agonist potency G-protein-coupling specificity 16,32
Gβγ and PLCβ1 Signaling complex formation 13
calmodulin Reverses PIP3-mediated GAP inhibition 46
spinophilin Scaffolding 35,61
δ receptor G-protein-coupling specificity 16,25,32
PAR4 27
mGlu5 receptor 60
COPI (protein complex) 57
Associated Protein Comments
Affinity for Gαq is lower than that for Gαi.

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
RGS4 inhibitor 11b Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.8 pIC50 59
⤷ pIC50 7.8 (IC50 1.44x10-8 M) [59]
Description: Inhibition of Gαo binding
CCG-50014 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.5 pIC50 5,59
⤷ pIC50 7.5 (IC50 3.01x10-8 M) [5,59]
Description: Inhibition of Gαo binding.
CCG-203920 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.3 pIC50 59
⤷ pIC50 7.3 (IC50 5.43x10-8 M) [59]
Description: Inhibition of Gαo binding
CCG-63808 Small molecule or natural product Hs Inhibition 5.0 – 5.8 pIC50 4
⤷ pIC50 5.0 – 5.8 (IC50 1x10-5 – 1.4x10-6 M) [4]
Description: Inhibition of Gαo binding. The higher affinity value was measured using TR-FRET, the lower value using flow cytometry protein interaction assay (FCPIA).
CCG-63802 Small molecule or natural product Hs Inhibition 5.1 – 5.7 pIC50 4
⤷ pIC50 5.1 – 5.7 (IC50 9x10-6 – 1.9x10-6 M) [4]
Description: Inhibition of Gαo binding. The higher affinity value was measured using TR-FRET, the lower value using flow cytometry protein interaction assay (FCPIA).
(4Z)-1-(3-fluorophenyl)-4-(2-oxo-1H-indol-3-ylidene)pyrazolidine-3,5-dione Small molecule or natural product Hs Inhibition 5.1 pIC50 56
⤷ pIC50 5.1 (IC50 8.2x10-6 M) [56]
CCG-4986 Small molecule or natural product Hs Inhibition 4.7 – 5.4 pIC50 28,47-48
⤷ pIC50 4.7 – 5.4 (IC50 1.8x10-5 – 4.2x10-6 M) [28,47-48]
Description: Inhibition of Gαo binding.
YJ34 Peptide Rn Inhibition 4.6 – 5.1 pIC50 24,49
⤷ pIC50 4.6 – 5.1 (IC50 2.6x10-5 – 9x10-6 M) [24,49]
Description: Inhibition of Gαo binding.
(5Z)-5-[(5-bromothiophen-2-yl)methylidene]-1-methyl-2-sulfanylidene-1,3-diazinane-4,6-dione Small molecule or natural product Hs Inhibition 4.8 pIC50 56
⤷ pIC50 4.8 (IC50 1.53x10-5 M) [56]
(5E)-1-(4-fluorophenyl)-5-[(5-methylthiophen-2-yl)methylidene]-2-sulfanylidene-1,3-diazinane-4,6-dione Small molecule or natural product Hs Inhibition 4.7 pIC50 56
⤷ pIC50 4.7 (IC50 1.83x10-5 M) [56]
(5Z)-1-(2-fluorophenyl)-2-sulfanylidene-5-(thiophen-2-ylmethylidene)-1,3-diazinane-4,6-dione Small molecule or natural product Hs Inhibition 4.6 pIC50 56
⤷ pIC50 4.6 (IC50 2.75x10-5 M) [56]
5nd Peptide Rn Inhibition 4.6 pIC50 50
⤷ pIC50 4.6 (IC50 2.8x10-5 M) [50]
Description: Inhibition of Gαo binding.
View species-specific inhibitor tables
Tissue Distribution Click here for help
High expression in brain, low/moderate expression in heart. Within brain: gyrus areas of cortex and hippocampus, hippocampus, putamen, and striatum.
Species:  Human
Technique:  Quantitative RT-PCR.
References:  30
Lung, lung epithelium
Species:  Human
Technique:  Immunohistochemistry, immunofluorescence, Western blot
References:  20,62
Vascular smooth muscle
Species:  Mouse
Technique:  mRNA Immunoprecipitation, Western blot, immunohistochemistry
References:  34
Lung, lung epithelium
Species:  Mouse
Technique:  Western blot, immunohistochemistry
References:  38,62
Ventral posterolateral thalamus, prefrontal cortex
Species:  Mouse
Technique:  Western blot
References:  1,36
Cortex, striatum, thalamus, hippocampus, primary cortical neurons
Species:  Rat
Technique:  In situ hybridisation, qRT-PCR, fluorescent in situ hybridisation
References:  14,17
Functional Assays Click here for help
Malachite Green Assay.
Species:  Rat
Tissue:  Biochemical assay.
Response measured:  Increase in free inorganic phosphate; measuring GTPase activity.
References:  41,56
Fluo4 NW calcium signaling assay.
Species:  Human
Tissue:  HEK-293 FlpIn-TREx; HEK-293T cells.
Response measured:  RGS4-mediated decrease in muscarinic M3 receptor-induced calcium transient.
References:  6,56
TR-FRET (assayed in human and rat).
Species:  Human
Tissue:  Biochemical assay.
Response measured:  Assay measuring protein-protein interaction between RGS4 and Gα.
References:  4
Transcreener GDP assay.
Species:  Human
Tissue:  Biochemical asay.
Response measured:  Measuring GTPase activity.
References:  65
Single turnover GTPase assay (measured in human and rat).
Species:  Human
Tissue:  Biochemical assay.
Response measured:  Measuring GTPase activity using γ[32P]GTP.
References:  48-49,56
Flow cytometry protein interaction assay.
Species:  Rat
Tissue:  Biochemical assay.
Response measured:  Fluorophore-labeled Gα binds to biotinylated RGS4 linked to LumAvidin beads; measurement of bead-associated fluorescence. 
References:  48
Physiological Functions Click here for help
Limits opioid-induced analgesia.
Species:  Mouse
Tissue:  Central nervous system (CNS).
References:  15
Inhibits phenylephrine- and endothelin-1-mediated signaling.
Species:  Rat
Tissue:  Cardiomyocytes.
References:  58
Regulates parasympathetic signaling in sinoatrial node.
Species:  Mouse
Tissue:  Heart, sinoatrial node.
References:  11
Negatively regulates insulin release, in vitro and in vivo.
Species:  Mouse
Tissue:  Pancreatic beta cells.
References:  52
Attenuates Gq-mediated PLCβ activation.
Species:  Human
Tissue:  Recombinant cells (NG-108).   
References:  21
Can accelerate activation and desensitization of GIRK channels.
Species:  Human
Tissue:  Exogenous expression in Xenopus oocytes.
References:  10
Inhibits intracellular Ca2+ signaling; inhibits PGE2 synthesis
Species:  Mouse
Tissue:  Lung
References:  62
Promotes BDNF signaling via suppression of miR-16 and promotes AKT signaling
Species:  Human
Tissue:  Recombinant cells (H1299 and PC9)
References:  20
Inhibits von Willebrand factor (VWF) secretion
Species:  Human
Tissue:  Primary cell culture (HUVECs)
References:  45
Inhibits glutamatergic signaling
Species:  Mouse
Tissue:  Central nervous system
References:  22,26
Physiological Consequences of Altering Gene Expression Click here for help
RGS4 knockout mice have increased PGE(2)-induced Muc5ac production.
Species:  Mouse
Tissue:  Airway.
Technique:  Gene knockout.
References:  55
RGS4 knockout mice have lower bodyweight and shorter duration before falling off of rotating rod.
Species:  Mouse
Tissue: 
Technique:  Gene knockout.
References:  18
Exogenous RGS4 expression in MDA-MB-231 cells slows tumor growth, by inhibiting tumor growth, and suppressing invasiveness.
Species:  Human
Tissue:  MDA-MB-231, implanted in mouse (xenograft).
Technique: 
References:  63
RGS4 knockout mice are more sensitive to CsA-induced renal failure.
Species:  Mouse
Tissue:  Kidney.
Technique:  Gene knockout.
References:  53
Involved in the generation of abnormal involuntary movements (AIMs) in the unilateral 6-OHDA-lesioned rat model of Parkinson's disease. RGS4 mRNA is elevated by L-DOPA treatment and suppressing this elevation during L-DOPA priming reduces the induction of AIMs.
Species:  Rat
Tissue:  Striatum.
Technique:  RNA interference.
References:  29
Involved in the generation of abnormal involuntary movements in the unilateral 6-OHDA-lesioned rat and mouse models of Parkinson's disease. In contrast to wild-type mice, RGS4⁻/⁻ mice exhibited normal eCB-LTD after dopamine depletion and were significantly less impaired in the 6-OHDA model of Parkinson's disease.    
Species:  Mouse
Tissue:  Striatum.
Technique:  Gene knockout.
References:  33
Loss of RGS4 promotes abnormal calcium release and is associated with atrial fibrillation. Attributed to enhanced activity in the Gαq/11- IP3 pathway resulting in abnormal Ca2+ release and corresponding electrical events.
Species:  Mouse
Tissue:  Heart, atrial cells.
Technique:  Gene knockout.
References:  44
RGS4 overexpression in mice reduces allergen-induced airway resistance and constriction in response to methacholine
Species:  Mouse
Tissue:  Lung
Technique: 
References:  37
RGS4 knockdown in mice susceptible to diet-induce-obesity reduces food intake
Species:  Mouse
Tissue:  Dorsal striatum
Technique:  siRNA
References:  39
RGS4 knockdown mice display increased sensitivity to morphine via enhanced glutamate receptor signaling
Species:  Mouse
Tissue:  Nucleus accumbens
Technique:  Lentiviral shRNA
References:  37
Male, but not female, RGS4 knockout mice displayed reduced condition-place preference in response to cocaine treatment
Species:  Mouse
Tissue: 
Technique: 
References:  51
RGS4 knockdown in mice induces dysfunction of cysteine/glutamate transporter system resulting in schizophrenic behaviors
Species:  Mouse
Tissue:  Prefrontal cortex
Technique:  Lentiviral shRNA
References:  22
RGS4 knockout in mice enhances recovery in chronic pain models
Species:  Mouse
Tissue:  Ventral posterolateral thalamus
Technique:  HTT flox/flox cre-inducible knockdown, RGS4 KO mice
References:  1
RGS4 knockdown decreases matrix metalloproteinase-2 expression and enhances apoptosis marker expression
Species:  Mouse
Tissue:  Patient-derived tumor cell lines (GSC20, GSC28)
Technique:  CRISPR-Cas9
References:  19
Xenobiotics Influencing Gene Expression Click here for help
RGS4 protein levels are increased by inhibitors of the proteasome, such as MG-132.   
Species:  Human
Tissue:  HEK-293 cells.
Technique:  Western blot and PathHunter ProLabel β-gal complementation assay.
References:  6,54
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Parkinson Disease
Synonyms: Parkinson's disease [Disease Ontology: DOID:14330]
Disease Ontology: DOID:14330
OMIM: 168600
References:  29,33
Disease:  Schizophrenia
Disease Ontology: DOID:5419
OMIM: 181500
Orphanet: ORPHA3140
References:  8-9,40,42
Biologically Significant Variants Click here for help
Type:  Splice variant
Species:  Human
Description:  Reduction in RGS4 isoform 3 splice variant associated with schizophrenia.
Amino acids:  187
Protein accession:  NP_001106851
References:  12
Type:  Single nucleotide polymorphism
Species:  Human
Description:  The RGS4 3′ UTR SNP, rs10759 is associated with risk of bladder cancer.
SNP accession:  rs10759
References:  31
Type:  Single nucleotide polymorphism
Species:  Human
Description:  The RGS4 promoter-region SNP, rs12041948 is associated with increased risk of schizophrenia in the northern Chinese Han population
SNP accession:  rs12041948
References:  64

References

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1. Avrampou K, Pryce KD, Ramakrishnan A, Sakloth F, Gaspari S, Serafini RA, Mitsi V, Polizu C, Swartz C, Ligas B et al.. (2019) RGS4 Maintains Chronic Pain Symptoms in Rodent Models. J Neurosci, 39 (42): 8291-8304. [PMID:31308097]

2. Berman DM, Kozasa T, Gilman AG. (1996) The GTPase-activating protein RGS4 stabilizes the transition state for nucleotide hydrolysis. J Biol Chem, 271 (44): 27209-12. [PMID:8910288]

3. Berman DM, Wilkie TM, Gilman AG. (1996) GAIP and RGS4 are GTPase-activating proteins for the Gi subfamily of G protein alpha subunits. Cell, 86 (3): 445-52. [PMID:8756726]

4. Blazer LL, Roman DL, Chung A, Larsen MJ, Greedy BM, Husbands SM, Neubig RR. (2010) Reversible, allosteric small-molecule inhibitors of regulator of G protein signaling proteins. Mol Pharmacol, 78 (3): 524-33. [PMID:20571077]

5. Blazer LL, Zhang H, Casey EM, Husbands SM, Neubig RR. (2011) A nanomolar-potency small molecule inhibitor of regulator of G-protein signaling proteins. Biochemistry, 50 (15): 3181-92. [PMID:21329361]

6. Bodenstein J, Sunahara RK, Neubig RR. (2007) N-terminal residues control proteasomal degradation of RGS2, RGS4, and RGS5 in human embryonic kidney 293 cells. Mol Pharmacol, 71 (4): 1040-50. [PMID:17220356]

7. Cervantes-Villagrana RD, Adame-García SR, García-Jiménez I, Color-Aparicio VM, Beltrán-Navarro YM, König GM, Kostenis E, Reyes-Cruz G, Gutkind JS, Vázquez-Prado J. (2019) Gβγ signaling to the chemotactic effector P-REX1 and mammalian cell migration is directly regulated by Gαq and Gα13 proteins. J Biol Chem, 294 (2): 531-546. [PMID:30446620]

8. Chen X, Dunham C, Kendler S, Wang X, O'Neill FA, Walsh D, Kendler KS. (2004) Regulator of G-protein signaling 4 (RGS4) gene is associated with schizophrenia in Irish high density families. Am J Med Genet B Neuropsychiatr Genet, 129B (1): 23-6. [PMID:15274033]

9. Chowdari KV, Mirnics K, Semwal P, Wood J, Lawrence E, Bhatia T, Deshpande SN, B K T, Ferrell RE, Middleton FA et al.. (2002) Association and linkage analyses of RGS4 polymorphisms in schizophrenia. Hum Mol Genet, 11 (12): 1373-80. [PMID:12023979]

10. Chuang HH, Yu M, Jan YN, Jan LY. (1998) Evidence that the nucleotide exchange and hydrolysis cycle of G proteins causes acute desensitization of G-protein gated inward rectifier K+ channels. Proc Natl Acad Sci USA, 95 (20): 11727-32. [PMID:9751733]

11. Cifelli C, Rose RA, Zhang H, Voigtlaender-Bolz J, Bolz SS, Backx PH, Heximer SP. (2008) RGS4 regulates parasympathetic signaling and heart rate control in the sinoatrial node. Circ Res, 103 (5): 527-35. [PMID:18658048]

12. Ding L, Hegde AN. (2009) Expression of RGS4 splice variants in dorsolateral prefrontal cortex of schizophrenic and bipolar disorder patients. Biol Psychiatry, 65 (6): 541-5. [PMID:19041089]

13. Dowal L, Elliott J, Popov S, Wilkie TM, Scarlata S. (2001) Determination of the contact energies between a regulator of G protein signaling and G protein subunits and phospholipase C beta 1. Biochemistry, 40 (2): 414-21. [PMID:11148035]

14. Ehses J, Fernández-Moya SM, Schröger L, Kiebler MA. (2021) Synergistic regulation of Rgs4 mRNA by HuR and miR-26/RISC in neurons. RNA Biol, 18 (7): 988-998. [PMID:32779957]

15. Garzón J, Rodríguez-Muñoz M, de la Torre-Madrid E, Sánchez-Blázquez P. (2005) Effector antagonism by the regulators of G protein signalling (RGS) proteins causes desensitization of mu-opioid receptors in the CNS. Psychopharmacology (Berl.), 180 (1): 1-11. [PMID:15830230]

16. Georgoussi Z, Leontiadis L, Mazarakou G, Merkouris M, Hyde K, Hamm H. (2006) Selective interactions between G protein subunits and RGS4 with the C-terminal domains of the mu- and delta-opioid receptors regulate opioid receptor signaling. Cell Signal, 18 (6): 771-82. [PMID:16120478]

17. Gold SJ, Ni YG, Dohlman HG, Nestler EJ. (1997) Regulators of G-protein signaling (RGS) proteins: region-specific expression of nine subtypes in rat brain. J Neurosci, 17 (20): 8024-37. [PMID:9315921]

18. Grillet N, Pattyn A, Contet C, Kieffer BL, Goridis C, Brunet JF. (2005) Generation and characterization of Rgs4 mutant mice. Mol Cell Biol, 25 (10): 4221-8. [PMID:15870291]

19. Guda MR, Velpula KK, Asuthkar S, Cain CP, Tsung AJ. (2020) Targeting RGS4 Ablates Glioblastoma Proliferation. Int J Mol Sci, 21 (9). [PMID:32392739]

20. He Z, Yu L, Luo S, Li Q, Huang S, An Y. (2019) RGS4 Regulates Proliferation And Apoptosis Of NSCLC Cells Via microRNA-16 And Brain-Derived Neurotrophic Factor. Onco Targets Ther, 12: 8701-8714. [PMID:31695428]

21. Heximer SP, Watson N, Linder ME, Blumer KJ, Hepler JR. (1997) RGS2/G0S8 is a selective inhibitor of Gqalpha function. Proc Natl Acad Sci USA, 94 (26): 14389-93. [PMID:9405622]

22. Huang MW, Lin YJ, Chang CW, Lei FJ, Ho EP, Liu RS, Shyu WC, Hsieh CH. (2018) RGS4 deficit in prefrontal cortex contributes to the behaviors related to schizophrenia via system xc--mediated glutamatergic dysfunction in mice. Theranostics, 8 (17): 4781-4794. [PMID:30279737]

23. Jaén C, Doupnik CA. (2006) RGS3 and RGS4 differentially associate with G protein-coupled receptor-Kir3 channel signaling complexes revealing two modes of RGS modulation. Precoupling and collision coupling. J Biol Chem, 281 (45): 34549-60. [PMID:16973624]

24. Jin Y, Zhong H, Omnaas JR, Neubig RR, Mosberg HI. (2004) Structure-based design, synthesis, and pharmacologic evaluation of peptide RGS4 inhibitors. J Pept Res, 63 (2): 141-6. [PMID:15009535]

25. Karoussiotis C, Marti-Solano M, Stepniewski TM, Symeonof A, Selent J, Georgoussi Z. (2020) A highly conserved δ-opioid receptor region determines RGS4 interaction. FEBS J, 287 (4): 736-748. [PMID:31386272]

26. Kim J, Lee S, Kang S, Jeon TI, Kang MJ, Lee TH, Kim YS, Kim KS, Im HI, Moon C. (2018) Regulator of G-Protein Signaling 4 (RGS4) Controls Morphine Reward by Glutamate Receptor Activation in the Nucleus Accumbens of Mouse Brain. Mol Cells, 41 (5): 454-464. [PMID:29754475]

27. Kim Y, Ghil S. (2020) Regulators of G-protein signaling, RGS2 and RGS4, inhibit protease-activated receptor 4-mediated signaling by forming a complex with the receptor and Gα in live cells. Cell Commun Signal, 18 (1): 86. [PMID:32517689]

28. Kimple AJ, Willard FS, Giguère PM, Johnston CA, Mocanu V, Siderovski DP. (2007) The RGS protein inhibitor CCG-4986 is a covalent modifier of the RGS4 Galpha-interaction face. Biochim Biophys Acta, 1774 (9): 1213-20. [PMID:17660054]

29. Ko WK, Martin-Negrier ML, Bezard E, Crossman AR, Ravenscroft P. (2014) RGS4 is involved in the generation of abnormal involuntary movements in the unilateral 6-OHDA-lesioned rat model of Parkinson's disease. Neurobiol Dis, 70: 138-48. [PMID:24969021]

30. Larminie C, Murdock P, Walhin JP, Duckworth M, Blumer KJ, Scheideler MA, Garnier M. (2004) Selective expression of regulators of G-protein signaling (RGS) in the human central nervous system. Brain Res Mol Brain Res, 122 (1): 24-34. [PMID:14992813]

31. Lee EK, Ye Y, Kamat AM, Wu X. (2013) Genetic variations in regulator of G-protein signaling (RGS) confer risk of bladder cancer. Cancer, 119 (9): 1643-51. [PMID:23529717]

32. Leontiadis LJ, Papakonstantinou MP, Georgoussi Z. (2009) Regulator of G protein signaling 4 confers selectivity to specific G proteins to modulate mu- and delta-opioid receptor signaling. Cell Signal, 21 (7): 1218-28. [PMID:19324084]

33. Lerner TN, Kreitzer AC. (2012) RGS4 is required for dopaminergic control of striatal LTD and susceptibility to parkinsonian motor deficits. Neuron, 73 (2): 347-59. [PMID:22284188]

34. Liu S, Jiang X, Lu H, Xing M, Qiao Y, Zhang C, Zhang W. (2020) HuR (Human Antigen R) Regulates the Contraction of Vascular Smooth Muscle and Maintains Blood Pressure. Arterioscler Thromb Vasc Biol, 40 (4): 943-957. [PMID:32075416]

35. Liu W, Yuen EY, Allen PB, Feng J, Greengard P, Yan Z. (2006) Adrenergic modulation of NMDA receptors in prefrontal cortex is differentially regulated by RGS proteins and spinophilin. Proc Natl Acad Sci USA, 103 (48): 18338-43. [PMID:17101972]

36. Lur G, Fariborzi M, Higley MJ. (2019) Ketamine disrupts neuromodulatory control of glutamatergic synaptic transmission. PLoS One, 14 (3): e0213721. [PMID:30865708]

37. Madigan LA, Wong GS, Gordon EM, Chen WS, Balenga N, Koziol-White CJ, Panettieri Jr RA, Levine SJ, Druey KM. (2018) RGS4 Overexpression in Lung Attenuates Airway Hyperresponsiveness in Mice. Am J Respir Cell Mol Biol, 58 (1): 89-98. [PMID:28853915]

38. Meng X, Sun X, Zhang Y, Shi H, Deng W, Liu Y, Wang G, Fang P, Yang S. (2018) PPARγ Agonist PGZ Attenuates OVA-Induced Airway Inflammation and Airway Remodeling via RGS4 Signaling in Mouse Model. Inflammation, 41 (6): 2079-2089. [PMID:30022363]

39. Michaelides M, Miller ML, Egervari G, Primeaux SD, Gomez JL, Ellis RJ, Landry JA, Szutorisz H, Hoffman AF, Lupica CR et al.. (2020) Striatal Rgs4 regulates feeding and susceptibility to diet-induced obesity. Mol Psychiatry, 25 (9): 2058-2069. [PMID:29955167]

40. Mirnics K, Middleton FA, Stanwood GD, Lewis DA, Levitt P. (2001) Disease-specific changes in regulator of G-protein signaling 4 (RGS4) expression in schizophrenia. Mol Psychiatry, 6 (3): 293-301. [PMID:11326297]

41. Monroy CA, Mackie DI, Roman DL. (2013) A high throughput screen for RGS proteins using steady state monitoring of free phosphate formation. PLoS ONE, 8 (4): e62247. [PMID:23626793]

42. Morris DW, Rodgers A, McGhee KA, Schwaiger S, Scully P, Quinn J, Meagher D, Waddington JL, Gill M, Corvin AP. (2004) Confirming RGS4 as a susceptibility gene for schizophrenia. Am J Med Genet B Neuropsychiatr Genet, 125B (1): 50-3. [PMID:14755443]

43. Moy FJ, Chanda PK, Cockett MI, Edris W, Jones PG, Mason K, Semus S, Powers R. (2000) NMR structure of free RGS4 reveals an induced conformational change upon binding Galpha. Biochemistry, 39 (24): 7063-73. [PMID:10852703]

44. Opel A, Nobles M, Montaigne D, Finlay M, Anderson N, Breckenridge R, Tinker A. (2015) Absence of the Regulator of G-protein Signaling, RGS4, Predisposes to Atrial Fibrillation and Is Associated with Abnormal Calcium Handling. J Biol Chem, 290 (31): 19233-44. [PMID:26088132]

45. Patella F, Cutler DF. (2020) RGS4 controls secretion of von Willebrand factor to the subendothelial matrix. J Cell Sci, 133 (14). [PMID:32576664]

46. Popov SG, Krishna UM, Falck JR, Wilkie TM. (2000) Ca2+/Calmodulin reverses phosphatidylinositol 3,4, 5-trisphosphate-dependent inhibition of regulators of G protein-signaling GTPase-activating protein activity. J Biol Chem, 275 (25): 18962-8. [PMID:10747990]

47. Roman DL, Blazer LL, Monroy CA, Neubig RR. (2010) Allosteric inhibition of the regulator of G protein signaling-Galpha protein-protein interaction by CCG-4986. Mol Pharmacol, 78 (3): 360-5. [PMID:20530129]

48. Roman DL, Talbot JN, Roof RA, Sunahara RK, Traynor JR, Neubig RR. (2007) Identification of small-molecule inhibitors of RGS4 using a high-throughput flow cytometry protein interaction assay. Mol Pharmacol, 71 (1): 169-75. [PMID:17012620]

49. Roof RA, Jin Y, Roman DL, Sunahara RK, Ishii M, Mosberg HI, Neubig RR. (2006) Mechanism of action and structural requirements of constrained peptide inhibitors of RGS proteins. Chem Biol Drug Des, 67 (4): 266-74. [PMID:16629824]

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51. Rorabaugh BR, Rose MJ, Stoops TS, Stevens AA, Seeley SL, D'Souza MS. (2018) Regulators of G-protein signaling 2 and 4 differentially regulate cocaine-induced rewarding effects. Physiol Behav, 195: 9-19. [PMID:30036561]

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