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regulator of G-protein signaling 2

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Target id: 2808

Nomenclature: regulator of G-protein signaling 2

Abbreviated Name: RGS2

Family: R4 family

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 211 1q31.2 RGS2 regulator of G protein signaling 2
Mouse - 211 1 62.56 cM Rgs2 regulator of G-protein signaling 2
Rat - 211 13q21 Rgs2 regulator of G-protein signaling 2
Previous and Unofficial Names Click here for help
G0S8 (human) | G0/G1 switch regulatory protein 8 | cell growth-inhibiting gene 31 protein
Database Links Click here for help
Alphafold P41220 (Hs), O08849 (Mm), Q9JHX0 (Rn)
CATH/Gene3D 1.10.196.10
Ensembl Gene ENSG00000116741 (Hs), ENSMUSG00000026360 (Mm), ENSRNOG00000003687 (Rn)
Entrez Gene 5997 (Hs), 19735 (Mm), 84583 (Rn)
Human Protein Atlas ENSG00000116741 (Hs)
KEGG Gene hsa:5997 (Hs), mmu:19735 (Mm), rno:84583 (Rn)
OMIM 600861 (Hs)
Pharos P41220 (Hs)
RefSeq Nucleotide NM_002923 (Hs), NM_009061 (Mm), NM_053453 (Rn)
RefSeq Protein NP_002914 (Hs), NP_033087 (Mm), NP_445905 (Rn)
UniProtKB P41220 (Hs), O08849 (Mm), Q9JHX0 (Rn)
Wikipedia RGS2 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Structure of the regulator of G-protein signaling domain of RGS2.
PDB Id:  2AF0
Resolution:  2.3Å
Species:  Human
References:  58
Image of receptor 3D structure from RCSB PDB
Description:  Structure of human regulator of G protein signaling 2 (RGS2) in complex with murine Gαq(R183C)
PDB Id:  4EKD
Resolution:  2.71Å
Species:  Human
References:  37
Associated Proteins Click here for help
G Proteins
Name References
Gαi/0
Gαq/11
Gαq13 17
Gαq15 19
Interacting Proteins
Name Effect References
Nek7 Mitotic spindle organization. 6
leucine rich repeat kinase 2 Control of neuronal process length, protective against neuronal toxicity. 8
TRPV6 Modulates channel activity. 52
eIF2Bε Controls protein synthesis. 38
Protein kinase G (PKG) 1 RGS2 phosphorylation, blunting RGS2 degradation, promotes RGS2 membrane localization. 41
adenylyl cyclase Inhibits cAMP production. 49,51
α1A-adrenoceptor Inhibition of α1A-adrenoceptor signaling. 13
M1 receptor Inhibits M1 mAChR-mediated signalling (carbachol-stimulated PIP2 hydrolysis and inositol 1,4,5-trisphosphate accumulation). 1
Protein Kinase C RGS2 phosphorylation, inhibition of RGS2 GAP activity 5
FBXO44 Recognition component of E3 ligase that facilitates RGS2 ubiquitination 56
PAR1 Inhibition of PAR1 signaling 10
PAR4 Inhibition of PAR4 signaling in presence of Gαq 22
κ receptor Inhibition of κ opioid receptor signaling, selective recruitment of Gαi subtypes 43
Tissue Distribution Click here for help
Prostate
Species:  Human
Technique:  Immunohistochemistry, RT-PCR, Western blot
References:  29-30
Heart.
Species:  Human
Technique:  Western blot.
References:  59
Brain, heart, lung, kidney, intestine, lymphocyte, placenta, testis.
Species:  Human
Technique:  RT-PCR, RNAseq
References:  26,44
Breast
Species:  Human
Technique:  Immunohistochemistry
References:  62
Heart, vascular smooth muscle
Species:  Mouse
Technique:  RT-PCR, Western blot, mRNA immunoprecipitation, immunohistochemistry
References:  31,54
Brain, heart, lung.
Species:  Mouse
Technique:  Western blot., RT-PCR
References:  20,45,66
Heart, brain, spleen, lung, skeletal muscle, kidney, testis, adrenal gland, ovary, uterus, placenta, intestine.
Species:  Mouse
Technique:  Northern blot, RT-PCR, 31865781
References:  4,24-25,44,52
Lung
Species:  Mouse
Technique:  RT-PCR, Western blot
References:  9
Adipose tissue
Species:  Mouse
Technique:  RT-PCR
References:  23
Osteoblast.
Species:  Mouse
Technique:  Immunofluorescence.
References:  50
Brain, heart, spleen, liver, skeletal muscle, kidney, and testis.
Species:  Rat
Technique:  Northern blot.
References:  35
Heart.
Species:  Rat
Technique:  Western blot.
References:  55
Functional Assays Click here for help
ERK1/2 activation attenuation in response to both endothelin-1 and isoproterenol.
Species:  Rat
Tissue:  Neonatal ventricular cardiomyocytes.
Response measured:  Reduced ERK1/2 phosphorylation.
References:  39
G protein binding, accelerates GTP hydrolysis by Gqα and inhibition of Gqα-mediated activation of PLCβ
Species:  None
Tissue:  Biochemical assay with purified protein.
Response measured:  Rgs2 binds to Gq and inhibits accumulation of [3H]phosphatidyl inositol 1,4,5-trisphosphate (IP3) produced by phospholipase C-β1.
References:  16-17,19
Inhibition of carbachol-induced IP3 production.
Species:  Human
Tissue:  HEK293 cells.
Response measured:  Reduced IP3 production.
References:  16
Gq-mediated intracellular calcium mobilization.
Species:  Human
Tissue:  HEK293T cells.
Response measured:  Inhibit Ca2+ signaling by Gαq/11-coupled M3 mAChRs.
References:  2
Reduced cAMP stimulation in response to β adrenergic receptor activation by isoproterenol (NB human and rat studied).
Species:  Human
Tissue:  Neonatal ventricular cardiomyocytes or HEK293T cells.
Response measured:  Reduction of cAMP response.
References:  39,46
Physiological Functions Click here for help
Inhibit cell growth in vitro.
Species:  Human
Tissue:  MCF7 and HEK293T cells.
References:  33
Modulation of vasoconstrictor responses and blood pressure in vivo. (NB human and mouse studied).
Species:  Human
Tissue:  Cardiovascular system, kidney, peripheral blood mononuclear cells, fibroblasts.
References:  12,14,53,60
Regulation of bone formation by osteoblasts.
Species:  Mouse
Tissue:  Osteoblasts.
References:  50
RGS2 knockdown prevents quinpirole-induced D2R internalization and inhibits β-arrestin membrane dissociation
Species:  Mouse
Tissue:  Neuroblastoma N2A cell line
References:  32
RGS2 negatively regulates insulin secretion and β-cell apoptosis in mouse pancreas
Species:  Mouse
Tissue:  Pancreas
References:  7
Full-length RGS2 or only its eIF2B-binding domain expressed in NIH-3T3 fibroblasts enhance stress-response mediators ATF4 and CHOP mRNA and protein levels, independent of eIF2B phosphorylation.
Species:  Mouse
Tissue:  NIH-3T3 fibroblasts
References:  63
RGS2 positively modulates brown adipogenesis via inhibition of the Gαq-Rho-ROCK pathway, but negatively modulates brown adipogenesis via inhibition of G αs-stimulated adenylate cyclase.
Species:  Mouse
Tissue:  Adipose tissue
References:  23
Physiological Consequences of Altering Gene Expression Click here for help
RGS2 knock-out mice develop hypertension phenotype.
Species:  Mouse
Tissue: 
Technique:  Gene knock-out.
References:  11,15,60
RGS2 knock-out caused spontaneous airway hyper responsiveness in mice,
Species:  Mouse
Tissue:  Lung.
Technique:  Gene knock-out.
References:  64
RGS2 deficient mice display increased anxiety responses, depression-like behaviour, reduced T cell proliferation and IL-2 production.
Species:  Mouse
Tissue:  Brain, T cells.
Technique:  Gene knock-out.
References:  28,40
RGS2 deficient mice have enhanced susceptibility to atrial tachycardia/fibrillation (AT/F) via enhanced M3 muscarinic receptor activity.
Species:  Mouse
Tissue:  Heart.
Technique:  Gene knock-out.
References:  61
RGS2 mRNA and protein levels are elevated in mononuclear cells from patients with Bartter's/Gitelman's syndrome. These patients show hyporesponsiveness to pressor agonists, are hypo/normotensive, and display altered vascular tone regulation.
Species:  Human
Tissue:  Mononuclear cells.
Technique:  RT-PCR and Western blot.
References:  3
RGS2 deficiency worsens kidney fibrosis and inflammation following unilateral ureteral obstruction (UUO) in mice. RGS2 deletion in bone marrow aggravates UUO-induced kidney fibrosis.
Species:  Mouse
Tissue:  Kidney.
Technique:  Gene knock-out.
References: 
RGS2 suppresses breast cancer cell growth: high RGS2 expression in non-invasive cells, low expression in invasive cells. Invasiveness can be prevented by overexpression of RGS2.
Species:  Mouse
Tissue:  MCF10A and MCF7 cells.
Technique:  Gene over-expression
References:  33
RGS2 knockout mice show enhanced fear learning and behavioral markers of anxiety.
Species:  Mouse
Tissue:  Whole animal
Technique:  Gene Knockout
References:  45
RGS2 knockdown delays mouse embryo development and reduces expression of zygotic genes
Species:  Mouse
Tissue:  Embryo
Technique:  siRNA microinjection
References:  68
RGS2 knockdown or knockout impedes uterine artery blood flow and enhances resting uterine artery myogenic tone and sensitivity
Species:  Mouse
Tissue:  Uterine vasculature
Technique:  Gene knockout
References:  21
RGS2 knockout increases sensitivity to house dust mite-induced airway inflammation in mice
Species:  Mouse
Tissue:  Lung
Technique:  Gene Knockout
References:  9
RGS2 knockout mice display enhanced anxiolytic but reduced antidepressant response to nicotine treatment.
Species:  Mouse
Tissue:  Whole animal
Technique:  Gene Knockout
References:  48
RGS2 knockout mice have decreased mid-pregnancy uterine blood flow, increased mid-pregnancy uterine artery cross-sectional area, and increased mid-pregnancy GPCR-mediated vasoconstriction.
Species:  Mouse
Tissue:  Uterine vasculature
Technique:  Gene Knockout
References:  24
RGS2 overexpression in serotonergic neurons in WT or rescue in RGS2 knockout mice induces an aggressive behavioral phenotype
Species:  Mouse
Tissue:  Brain, whole animal
Technique:  Gene knockout, gene over-expression
References:  34
Reduced RGS2 mRNA expression is associated with preeclampsia in humans and is sufficient to cause it in mice
Species:  Human
Tissue:  Placenta
Technique: 
References:  44
RGS2 knockdown alleviates depression-like symptoms in mice
Species:  Mouse
Tissue:  Whole animal
Technique:  siRNA
References:  67
Xenobiotics Influencing Gene Expression Click here for help
Proteasome inhibitor (MG-132, lactacystin) or cardiotonic steroids (digoxin, ouabain) treatment increases protein levels.
Species:  Human
Tissue:  HEK293T, HEK293FT and MCF7 cells.
Technique:  Western blot, PathHunter ProLabel β-galactosidase complementation assay.
References:  2,33,55
Proteasome inhibitors (MG-132, lactacystin) or cardiotonic steroids (digoxin, ouabain) treatment increase protein levels.
Species:  Rat
Tissue:  Primary aortic vascular smooth muscle cells.
Technique:  Western blot.
References:  55
Protein kinase C activator (indolactam V, PMA) treatment increases protein levels.
Species:  Human
Tissue:  HEK293T cells.
Technique:  Western blot, PathHunter ProLabel β-galactosidase complementation assay.
References:  46
Protein kinase C activator (Indolactam V, PMA) treatment increases protein levels.
Species:  Rat
Tissue:  Primary aortic vascular smooth muscle cells.
Technique:  Western blot.
References:  46
Type 1α protein kinase G inhibitor (Rp-8-pCPT-cGMPS) treatment stabilizes RGS2 protein.
Species:  Mouse
Tissue:  A7r5 vascular smooth muscle cells.
Technique:  Western blot.
References:  41
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Anxiety
OMIM: 607834
Comments:  Anxiety and panic disorder.
References:  18,27,36,42,57
Disease:  Hypertension, essential
Disease Ontology: DOID:10825
OMIM: 145500
References:  15,47,60,65

References

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1. Bernstein LS, Ramineni S, Hague C, Cladman W, Chidiac P, Levey AI, Hepler JR. (2004) RGS2 binds directly and selectively to the M1 muscarinic acetylcholine receptor third intracellular loop to modulate Gq/11alpha signaling. J Biol Chem, 279 (20): 21248-56. [PMID:14976183]

2. 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]

3. Calò LA, Pagnin E, Davis PA, Sartori M, Ceolotto G, Pessina AC, Semplicini A. (2004) Increased expression of regulator of G protein signaling-2 (RGS-2) in Bartter's/Gitelman's syndrome. A role in the control of vascular tone and implication for hypertension. J Clin Endocrinol Metab, 89 (8): 4153-7. [PMID:15292363]

4. Chen C, Zheng B, Han J, Lin SC. (1997) Characterization of a novel mammalian RGS protein that binds to Galpha proteins and inhibits pheromone signaling in yeast. J Biol Chem, 272 (13): 8679-85. [PMID:9079700]

5. Cunningham ML, Waldo GL, Hollinger S, Hepler JR, Harden TK. (2001) Protein kinase C phosphorylates RGS2 and modulates its capacity for negative regulation of Galpha 11 signaling. J Biol Chem, 276 (8): 5438-44. [PMID:11063746]

6. de Souza EE, Hehnly H, Perez AM, Meirelles GV, Smetana JH, Doxsey S, Kobarg J. (2015) Human Nek7-interactor RGS2 is required for mitotic spindle organization. Cell Cycle, 14 (4): 656-67. [PMID:25664600]

7. Dong H, Zhang Y, Wang J, Kim DS, Wu H, Sjögren B, Gao W, Luttrell L, Wang H. (2017) Regulator of G protein signaling 2 is a key regulator of pancreatic β-cell mass and function. Cell Death Dis, 8 (5): e2821. [PMID:28542139]

8. Dusonchet J, Li H, Guillily M, Liu M, Stafa K, Derada Troletti C, Boon JY, Saha S, Glauser L, Mamais A et al.. (2014) A Parkinson's disease gene regulatory network identifies the signaling protein RGS2 as a modulator of LRRK2 activity and neuronal toxicity. Hum Mol Genet, 23 (18): 4887-905. [PMID:24794857]

9. George T, Bell M, Chakraborty M, Siderovski DP, Giembycz MA, Newton R. (2017) Protective Roles for RGS2 in a Mouse Model of House Dust Mite-Induced Airway Inflammation. PLoS One, 12 (1): e0170269. [PMID:28107494]

10. Ghil S, McCoy KL, Hepler JR. (2014) Regulator of G protein signaling 2 (RGS2) and RGS4 form distinct G protein-dependent complexes with protease activated-receptor 1 (PAR1) in live cells. PLoS One, 9 (4): e95355. [PMID:24743392]

11. Gross V, Tank J, Obst M, Plehm R, Blumer KJ, Diedrich A, Jordan J, Luft FC. (2005) Autonomic nervous system and blood pressure regulation in RGS2-deficient mice. Am J Physiol Regul Integr Comp Physiol, 288 (5): R1134-42. [PMID:15661972]

12. Gurley SB, Griffiths RC, Mendelsohn ME, Karas RH, Coffman TM. (2010) Renal actions of RGS2 control blood pressure. J Am Soc Nephrol, 21 (11): 1847-51. [PMID:20847141]

13. Hague C, Bernstein LS, Ramineni S, Chen Z, Minneman KP, Hepler JR. (2005) Selective inhibition of alpha1A-adrenergic receptor signaling by RGS2 association with the receptor third intracellular loop. J Biol Chem, 280 (29): 27289-95. [PMID:15917235]

14. Hercule HC, Tank J, Plehm R, Wellner M, da Costa Goncalves AC, Gollasch M, Diedrich A, Jordan J, Luft FC, Gross V. (2007) Regulator of G protein signalling 2 ameliorates angiotensin II-induced hypertension in mice. Exp Physiol, 92 (6): 1014-22. [PMID:17644703]

15. Heximer SP, Knutsen RH, Sun X, Kaltenbronn KM, Rhee MH, Peng N, Oliveira-dos-Santos A, Penninger JM, Muslin AJ, Steinberg TH et al.. (2003) Hypertension and prolonged vasoconstrictor signaling in RGS2-deficient mice. J Clin Invest, 111 (4): 445-52. [PMID:12588882]

16. Heximer SP, Srinivasa SP, Bernstein LS, Bernard JL, Linder ME, Hepler JR, Blumer KJ. (1999) G protein selectivity is a determinant of RGS2 function. J Biol Chem, 274 (48): 34253-9. [PMID:10567399]

17. 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]

18. Hohoff C, Weber H, Richter J, Domschke K, Zwanzger PM, Ohrmann P, Bauer J, Suslow T, Kugel H, Baumann C et al.. (2015) RGS2 ggenetic variation: association analysis with panic disorder and dimensional as well as intermediate phenotypes of anxiety. Am J Med Genet B Neuropsychiatr Genet, 168B (3): 211-22. [PMID:25740197]

19. Ingi T, Krumins AM, Chidiac P, Brothers GM, Chung S, Snow BE, Barnes CA, Lanahan AA, Siderovski DP, Ross EM et al.. (1998) Dynamic regulation of RGS2 suggests a novel mechanism in G-protein signaling and neuronal plasticity. J Neurosci, 18 (18): 7178-88. [PMID:9736641]

20. Jiang H, Xie Y, Abel PW, Wolff DW, Toews ML, Panettieri Jr RA, Casale TB, Tu Y. (2015) Regulator of G-Protein Signaling 2 Repression Exacerbates Airway Hyper-Responsiveness and Remodeling in Asthma. Am J Respir Cell Mol Biol, 53 (1): 42-9. [PMID:25368964]

21. Jie L, Owens EA, Plante LA, Fang Z, Rensing DT, Moeller KD, Osei-Owusu P. (2016) RGS2 squelches vascular Gi/o and Gq signaling to modulate myogenic tone and promote uterine blood flow. Physiol Rep, 4 (2). [PMID:26811058]

22. 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]

23. Klepac K, Yang J, Hildebrand S, Pfeifer A. (2019) RGS2: A multifunctional signaling hub that balances brown adipose tissue function and differentiation. Mol Metab, 30: 173-183. [PMID:31767169]

24. Koch JN, Dahlen SA, Owens EA, Osei-Owusu P. (2019) Regulator of G Protein Signaling 2 Facilitates Uterine Artery Adaptation During Pregnancy in Mice. J Am Heart Assoc, 8 (9): e010917. [PMID:31030617]

25. Kurrasch DM, Huang J, Wilkie TM, Repa JJ. (2004) Quantitative real-time polymerase chain reaction measurement of regulators of G-protein signaling mRNA levels in mouse tissues. Meth Enzymol, 389: 3-15. [PMID:15313556]

26. 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]

27. Leygraf A, Hohoff C, Freitag C, Willis-Owen SA, Krakowitzky P, Fritze J, Franke P, Bandelow B, Fimmers R, Flint J et al.. (2006) Rgs 2 gene polymorphisms as modulators of anxiety in humans?. J Neural Transm, 113 (12): 1921-5. [PMID:16736243]

28. Lifschytz T, Broner EC, Zozulinsky P, Slonimsky A, Eitan R, Greenbaum L, Lerer B. (2012) Relationship between Rgs2 gene expression level and anxiety and depression-like behaviour in a mutant mouse model: serotonergic involvement. Int J Neuropsychopharmacol, 15 (9): 1307-18. [PMID:22040681]

29. Linder A, Hagberg Thulin M, Damber JE, Welén K. (2018) Analysis of regulator of G-protein signalling 2 (RGS2) expression and function during prostate cancer progression. Sci Rep, 8 (1): 17259. [PMID:30467386]

30. Linder A, Larsson K, Welén K, Damber JE. (2020) RGS2 is prognostic for development of castration resistance and cancer-specific survival in castration-resistant prostate cancer. Prostate, 80 (11): 799-810. [PMID:32449815]

31. 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]

32. Luessen DJ, Hinshaw TP, Sun H, Howlett AC, Marrs G, McCool BA, Chen R. (2016) RGS2 modulates the activity and internalization of dopamine D2 receptors in neuroblastoma N2A cells. Neuropharmacology, 110 (Pt A): 297-307. [PMID:27528587]

33. Lyu JH, Park DW, Huang B, Kang SH, Lee SJ, Lee C, Bae YS, Lee JG, Baek SH. (2015) RGS2 suppresses breast cancer cell growth via a MCPIP1-dependent pathway. J Cell Biochem, 116 (2): 260-7. [PMID:25187114]

34. Mark MD, Wollenweber P, Gesk A, Kösters K, Batzke K, Janoschka C, Maejima T, Han J, Deneris ES, Herlitze S. (2019) RGS2 drives male aggression in mice via the serotonergic system. Commun Biol, 2: 373. [PMID:31633064]

35. Miles RR, Sluka JP, Santerre RF, Hale LV, Bloem L, Boguslawski G, Thirunavukkarasu K, Hock JM, Onyia JE. (2000) Dynamic regulation of RGS2 in bone: potential new insights into parathyroid hormone signaling mechanisms. Endocrinology, 141 (1): 28-36. [PMID:10614620]

36. Mouri K, Hishimoto A, Fukutake M, Nishiguchi N, Shirakawa O, Maeda K. (2010) Association study of RGS2 gene polymorphisms with panic disorder in Japanese. Kobe J Med Sci, 55 (5): E116-21. [PMID:20847599]

37. Nance MR, Kreutz B, Tesmer VM, Sterne-Marr R, Kozasa T, Tesmer JJ. (2013) Structural and functional analysis of the regulator of G protein signaling 2-gαq complex. Structure, 21 (3): 438-48. [PMID:23434405]

38. Nguyen CH, Ming H, Zhao P, Hugendubler L, Gros R, Kimball SR, Chidiac P. (2009) Translational control by RGS2. J Cell Biol, 186 (5): 755-65. [PMID:19736320]

39. Nunn C, Zou MX, Sobiesiak AJ, Roy AA, Kirshenbaum LA, Chidiac P. (2010) RGS2 inhibits beta-adrenergic receptor-induced cardiomyocyte hypertrophy. Cell Signal, 22 (8): 1231-9. [PMID:20362664]

40. Oliveira-Dos-Santos AJ, Matsumoto G, Snow BE, Bai D, Houston FP, Whishaw IQ, Mariathasan S, Sasaki T, Wakeham A, Ohashi PS et al.. (2000) Regulation of T cell activation, anxiety, and male aggression by RGS2. Proc Natl Acad Sci USA, 97 (22): 12272-7. [PMID:11027316]

41. Osei-Owusu P, Sun X, Drenan RM, Steinberg TH, Blumer KJ. (2007) Regulation of RGS2 and second messenger signaling in vascular smooth muscle cells by cGMP-dependent protein kinase. J Biol Chem, 282 (43): 31656-65. [PMID:17681944]

42. Otowa T, Shimada T, Kawamura Y, Sugaya N, Yoshida E, Inoue K, Yasuda S, Liu X, Minato T, Tochigi M et al.. (2011) Association of RGS2 variants with panic disorder in a Japanese population. Am J Med Genet B Neuropsychiatr Genet, 156B (4): 430-4. [PMID:21438143]

43. Papakonstantinou MP, Karoussiotis C, Georgoussi Z. (2015) RGS2 and RGS4 proteins: New modulators of the κ-opioid receptor signaling. Cell Signal, 27 (1): 104-14. [PMID:25289860]

44. Perschbacher KJ, Deng G, Sandgren JA, Walsh JW, Witcher PC, Sapouckey SA, Owens CE, Zhang SY, Scroggins SM, Pearson NA et al.. (2020) Reduced mRNA Expression of RGS2 (Regulator of G Protein Signaling-2) in the Placenta Is Associated With Human Preeclampsia and Sufficient to Cause Features of the Disorder in Mice. Hypertension, 75 (2): 569-579. [PMID:31865781]

45. Raab A, Popp S, Lesch KP, Lohse MJ, Fischer M, Deckert J, Hommers L. (2018) Increased fear learning, spatial learning as well as neophobia in Rgs2-/- mice. Genes Brain Behav, 17 (4): e12420. [PMID:28846187]

46. Raveh A, Schultz PJ, Aschermann L, Carpenter C, Tamayo-Castillo G, Cao S, Clardy J, Neubig RR, Sherman DH, Sjögren B. (2014) Identification of protein kinase C activation as a novel mechanism for RGS2 protein upregulation through phenotypic screening of natural product extracts. Mol Pharmacol, 86 (4): 406-16. [PMID:25086086]

47. Riddle EL, Rana BK, Murthy KK, Rao F, Eskin E, O'Connor DT, Insel PA. (2006) Polymorphisms and haplotypes of the regulator of G protein signaling-2 gene in normotensives and hypertensives. Hypertension, 47 (3): 415-20. [PMID:16432041]

48. Rorabaugh BR, Sprague L, Norman H, Seeley SL, D'Souza MS. (2018) Regulator of G protein signaling 2 differentially regulates nicotine-induced anxiolytic- and antidepressant-like effects in mice. Eur J Neurosci, 48 (5): 2110-2117. [PMID:30103281]

49. Roy AA, Baragli A, Bernstein LS, Hepler JR, Hébert TE, Chidiac P. (2006) RGS2 interacts with Gs and adenylyl cyclase in living cells. Cell Signal, 18 (3): 336-48. [PMID:16095880]

50. Roy AA, Nunn C, Ming H, Zou MX, Penninger J, Kirshenbaum LA, Dixon SJ, Chidiac P. (2006) Up-regulation of endogenous RGS2 mediates cross-desensitization between Gs and Gq signaling in osteoblasts. J Biol Chem, 281 (43): 32684-93. [PMID:16950788]

51. Salim S, Sinnarajah S, Kehrl JH, Dessauer CW. (2003) Identification of RGS2 and type V adenylyl cyclase interaction sites. J Biol Chem, 278 (18): 15842-9. [PMID:12604604]

52. Schoeber JP, Topala CN, Wang X, Diepens RJ, Lambers TT, Hoenderop JG, Bindels RJ. (2006) RGS2 inhibits the epithelial Ca2+ channel TRPV6. J Biol Chem, 281 (40): 29669-74. [PMID:16895908]

53. Semplicini A, Lenzini L, Sartori M, Papparella I, Calò LA, Pagnin E, Strapazzon G, Benna C, Costa R, Avogaro A et al.. (2006) Reduced expression of regulator of G-protein signaling 2 (RGS2) in hypertensive patients increases calcium mobilization and ERK1/2 phosphorylation induced by angiotensin II. J Hypertens, 24 (6): 1115-24. [PMID:16685212]

54. Sjögren B, Parra S, Atkins KB, Karaj B, Neubig RR. (2016) Digoxin-Mediated Upregulation of RGS2 Protein Protects against Cardiac Injury. J Pharmacol Exp Ther, 357 (2): 311-9. [PMID:26941169]

55. Sjögren B, Parra S, Heath LJ, Atkins KB, Xie ZJ, Neubig RR. (2012) Cardiotonic steroids stabilize regulator of G protein signaling 2 protein levels. Mol Pharmacol, 82 (3): 500-9. [PMID:22695717]

56. Sjögren B, Swaney S, Neubig RR. (2015) FBXO44-Mediated Degradation of RGS2 Protein Uniquely Depends on a Cullin 4B/DDB1 Complex. PLoS One, 10 (5): e0123581. [PMID:25970626]

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