Genomes and Genes
Summary: A large family of evolutionarily conserved proteins that function as negative regulators of HETEROTRIMERIC GTP-BINDING PROTEINS. RGS PROTEINS act by increasing the GTPase activity of the G alpha subunit of a heterotrimeric GTP-binding protein, causing it to revert to its inactive (GDP-bound) form.
- Li H, He C, Feng J, Zhang Y, Tang Q, Bian Z, et al. Regulator of G protein signaling 5 protects against cardiac hypertrophy and fibrosis during biomechanical stress of pressure overload. Proc Natl Acad Sci U S A. 2010;107:13818-23 pubmed publisher..These studies indicate that Rgs5 protein is a crucial component of the signaling pathway involved in cardiac remodeling and heart failure. ..
- Shankar S, Wilson M, DiVietro J, Mentink Kane M, Xie Z, Wynn T, et al. RGS16 attenuates pulmonary Th2/Th17 inflammatory responses. J Immunol. 2012;188:6347-56 pubmed publisher..Thus, RGS16-mediated confinement of T cells to Schistosome granulomas mitigates widespread cytokine-mediated pulmonary inflammation. ..
- Tsang S, Woo A, Zhu W, Xiao R. Deregulation of RGS2 in cardiovascular diseases. Front Biosci (Schol Ed). 2010;2:547-57 pubmed..These findings indicate that deregulation of RGS2 plays a crucial role in the pathogenesis of cardiovascular diseases, marking RGS2 as a potential therapeutic target or biomarker of hypertension or hypertensive heart diseases. ..
- Zielinski T, Kimple A, Hutsell S, Koeff M, Siderovski D, Lowery R. Two Galpha(i1) rate-modifying mutations act in concert to allow receptor-independent, steady-state measurements of RGS protein activity. J Biomol Screen. 2009;14:1195-206 pubmed publisherb>RGS proteins are critical modulators of G-protein-coupled receptor (GPCR) signaling given their ability to deactivate Galpha subunits via GTPase-accelerating protein (GAP) activity...
- Mackie D, Roman D. Development of a novel high-throughput screen and identification of small-molecule inhibitors of the G?-RGS17 protein-protein interaction using AlphaScreen. J Biomol Screen. 2011;16:869-77 pubmed publisher..report describes the first high-throughput screen for RGS17 inhibitors, as well as a novel paradigm adaptable to many other RGS proteins, which are emerging as attractive drug targets for modulating G-protein-coupled receptor signaling.
- Gunaje J, Bahrami A, Schwartz S, Daum G, Mahoney W. PDGF-dependent regulation of regulator of G protein signaling-5 expression and vascular smooth muscle cell functionality. Am J Physiol Cell Physiol. 2011;301:C478-89 pubmed publisher..These results demonstrate that RGS5 expression is a critical mediator of both VSMC contraction and potentially, arterial remodeling. ..
- Hendriks Balk M, van Loenen P, Hajji N, Michel M, Peters S, Alewijnse A. S1P receptor signalling and RGS proteins; expression and function in vascular smooth muscle cells and transfected CHO cells. Eur J Pharmacol. 2008;600:1-9 pubmed publisher..Therefore, we investigated the role of altered expression levels of RGS proteins in S1P receptor function in VSMCs and transfected CHO cells...
- Wang J, Xie Y, Wolff D, Abel P, Tu Y. DHHC protein-dependent palmitoylation protects regulator of G-protein signaling 4 from proteasome degradation. FEBS Lett. 2010;584:4570-4 pubmed publisher..Together, our findings revealed that DHHC proteins could regulate GPCR-mediated signaling by increasing RGS4 stability. ..
- Zhang J, Jeffrey B, Morgans C, Burke N, Haley T, Duvoisin R, et al. RGS7 and -11 complexes accelerate the ON-bipolar cell light response. Invest Ophthalmol Vis Sci. 2010;51:1121-9 pubmed publisher..RGS11 plays a role in the deactivation of Galphao, which precedes activation of the depolarizing current in ON-BPCs. RGS7 must also serve a role as changes in RGS7(Delta/Delta)/RGS11(-/-) mice were greater than those in RGS11(-/-) mice. ..
- Cao Y, Masuho I, Okawa H, Xie K, Asami J, Kammermeier P, et al. Retina-specific GTPase accelerator RGS11/G beta 5S/R9AP is a constitutive heterotrimer selectively targeted to mGluR6 in ON-bipolar neurons. J Neurosci. 2009;29:9301-13 pubmed publisher..These results suggest that the deactivation of mGluR6 cascade during the light response may require the contribution of multiple GTPase activating proteins. ..
- Hurst J, Mendpara N, Hooks S. Regulator of G-protein signalling expression and function in ovarian cancer cell lines. Cell Mol Biol Lett. 2009;14:153-74 pubmed publisher..We have recently reported that RGS proteins endogenously expressed in SKOV-3 ovarian cancer cells dramatically attenuate LPA stimulated cell signalling...
- Wu Y, Chuang H, Kou Y, Lee T, Lu S, Huang Y, et al. Regulation of LH receptor and PGF2alpha receptor signaling by the regulator of G protein signaling 2 (RGS2) in human and mouse granulosa cells. Chin J Physiol. 2008;51:282-91 pubmed..Thus, RGS2 expression was upregulated by LH receptor and FP receptor activation and modulation of partner receptor signaling by RGS2 may require RGS2 translocation from the nucleus to the plasma membrane. ..
- Chakir K, Zhu W, Tsang S, Woo A, Yang D, Wang X, et al. RGS2 is a primary terminator of ??-adrenergic receptor-mediated G(i) signaling. J Mol Cell Cardiol. 2011;50:1000-7 pubmed publisher..is accompanied by a selective upregulation of RGS2 in the absence of alterations in other major cardiac RGS proteins (RGS3-5) or G(s), G(i) or ?AR subtypes. Administration of a ?AR agonist, isoproterenol (ISO, 1...
- Jones J, Temple B, Jones A, Dohlman H. Functional reconstitution of an atypical G protein heterotrimer and regulator of G protein signaling protein (RGS1) from Arabidopsis thaliana. J Biol Chem. 2011;286:13143-50 pubmed publisher..Thus, despite profound differences in the mechanisms of activation, the Arabidopsis G protein is readily inactivated by its cognate RGS protein and forms a stable, GDP-bound, heterotrimeric complex similar to that found in animals. ..
- Waterson R, Thompson C, Mabe N, Kaur K, Talbot J, Neubig R, et al. G?(i2)-mediated protection from ischaemic injury is modulated by endogenous RGS proteins in the mouse heart. Cardiovasc Res. 2011;91:45-52 pubmed publisher..However, the role of RGS proteins in modulating cardioprotection has not been previously investigated...
- You M, Wang D, Liu P, Vikis H, James M, Lu Y, et al. Fine mapping of chromosome 6q23-25 region in familial lung cancer families reveals RGS17 as a likely candidate gene. Clin Cancer Res. 2009;15:2666-74 pubmed publisher..Human lung tumor cell proliferation and tumorigenesis in nude mice are inhibited upon knockdown of RGS17 levels. RGS17 is a major candidate for the familial lung cancer susceptibility locus on chromosome 6q23-25. ..
- Sandiford S, Slepak V. The Gbeta5-RGS7 complex selectively inhibits muscarinic M3 receptor signaling via the interaction between the third intracellular loop of the receptor and the DEP domain of RGS7. Biochemistry. 2009;48:2282-9 pubmed publisher..In addition to the RGS domain, which is responsible for GAP activity, most RGS proteins contain other distinct structural motifs...
- Xie K, Allen K, Kourrich S, Colón Saez J, Thomas M, Wickman K, et al. Gbeta5 recruits R7 RGS proteins to GIRK channels to regulate the timing of neuronal inhibitory signaling. Nat Neurosci. 2010;13:661-3 pubmed publisher..Our findings identify a compartmentalization mechanism that is critical for ensuring high temporal resolution of neuronal G protein signaling. ..
- Takimoto E, Koitabashi N, Hsu S, Ketner E, Zhang M, Nagayama T, et al. Regulator of G protein signaling 2 mediates cardiac compensation to pressure overload and antihypertrophic effects of PDE5 inhibition in mice. J Clin Invest. 2009;119:408-20 pubmed publisher..Thus, RGS2 is required for early myocardial compensation to pressure overload and mediates the initial antihypertrophic and cardioprotective effects of PDE5 inhibitors. ..
- Kaur K, Kehrl J, Charbeneau R, Neubig R. RGS-insensitive G? subunits: probes of G? subtype-selective signaling and physiological functions of RGS proteins. Methods Mol Biol. 2011;756:75-98 pubmed publisher..e., GTPase acceleration protein or GAP activity). The GAP activity of RGS proteins on the G?i and G?q family of G proteins can terminate signals initiated by both ? and ?? subunits...
- Bansal G, DiVietro J, Kuehn H, Rao S, Nocka K, Gilfillan A, et al. RGS13 controls g protein-coupled receptor-evoked responses of human mast cells. J Immunol. 2008;181:7882-90 pubmed..Several RGS proteins were expressed in mast cells including RGS13, which we previously showed inhibited IgE-mediated mast cell ..
- Li F, Murthy K, Khalili K, Hu W. Cloning and characterization of rabbit Rgs4 promoter in gut smooth muscle. Gene. 2010;451:45-53 pubmed publisher..Our studies provide an important basis for further understanding of Rgs4 regulation and function in different diseases. ..
- Xiao B, Zhang Y, Niu W, Gao P, Zhu D. Haplotype-based association of regulator of G-protein signaling 5 gene polymorphisms with essential hypertension and metabolic parameters in Chinese. Clin Chem Lab Med. 2009;47:1483-8 pubmed publisher..0001 and 0.0309). Multiple SNPs in combination in RGS5 may confer risk for hypertension. Our results also lend support for the effect of RGS5 SNPs on lipid metabolism. Further studies are warranted to find the causal SNPs in RGS5 for EH. ..
- Urano D, Jones J, Wang H, Matthews M, Bradford W, Bennetzen J, et al. G protein activation without a GEF in the plant kingdom. PLoS Genet. 2012;8:e1002756 pubmed publisher..Like grasses, non-vascular plants also appear to lack RGS proteins. However, unlike grasses, one representative non-vascular plant G? showed rapid GTP hydrolysis, likely ..
- Nunn C, Zhao P, Zou M, Summers K, Guglielmo C, Chidiac P. Resistance to age-related, normal body weight gain in RGS2 deficient mice. Cell Signal. 2011;23:1375-86 pubmed publisher..In conclusion this study points to RGS2 as being an important regulatory factor in controlling body weight and adipose function. ..
- Lerner T, Kreitzer A. RGS4 is required for dopaminergic control of striatal LTD and susceptibility to parkinsonian motor deficits. Neuron. 2012;73:347-59 pubmed publisher..Taken together, these results suggest that inhibition of RGS4 may be an effective nondopaminergic strategy for treating Parkinson's disease. ..
- Runne H, Regulier E, Kuhn A, Zala D, Gokce O, Perrin V, et al. Dysregulation of gene expression in primary neuron models of Huntington's disease shows that polyglutamine-related effects on the striatal transcriptome may not be dependent on brain circuitry. J Neurosci. 2008;28:9723-31 pubmed publisher
- Inoue Mochita M, Inoue T, Epstein D, Blumer K, Rao P. RGS2-deficient mice exhibit decreased intraocular pressure and increased retinal ganglion cell survival. Mol Vis. 2009;15:495-504 pubmed..These data indicate a potentially critical role for RGS2 in homeostasis of IOP and for retinal ganglion cell survival. ..
- Lee S, Simons S, Heldt S, Zhao M, Schroeder J, Vellano C, et al. RGS14 is a natural suppressor of both synaptic plasticity in CA2 neurons and hippocampal-based learning and memory. Proc Natl Acad Sci U S A. 2010;107:16994-8 pubmed publisher..These results demonstrate that RGS14 is a key regulator of signaling pathways linking synaptic plasticity in CA2 pyramidal neurons to hippocampal-based learning and memory but distinct from the canonical DG-CA3-CA1 circuit. ..
- Hu W, Li F, Mahavadi S, Murthy K. Upregulation of RGS4 expression by IL-1beta in colonic smooth muscle is enhanced by ERK1/2 and p38 MAPK and inhibited by the PI3K/Akt/GSK3beta pathway. Am J Physiol Cell Physiol. 2009;296:C1310-20 pubmed publisher..GSK3beta acts normally to augment the activation of the canonical NF-kappaB signaling. The PI3K/Akt/GSK3beta pathway attenuates IL-1beta-induced upregulation of RGS4 expression by inhibiting NF-kappaB activation. ..
- Roof R, Roman D, Clements S, Sobczyk Kojiro K, Blazer L, Ota S, et al. A covalent peptide inhibitor of RGS4 identified in a focused one-bead, one compound library screen. BMC Pharmacol. 2009;9:9 pubmed publisher..The distinct expression patterns and pathophysiologic regulation of RGS proteins suggest that inhibitors may have therapeutic potential...
- Hooks S, Callihan P, Altman M, Hurst J, Ali M, Murph M. Regulators of G-Protein signaling RGS10 and RGS17 regulate chemoresistance in ovarian cancer cells. Mol Cancer. 2010;9:289 pubmed publisher..RGS10 knock-down and RGS 10 and RGS17 overexpression blocked LPA mediated activation of AKT, suggesting that RGS proteins may blunt AKT survival pathways...
- Jin Y, An X, Ye Z, Cully B, Wu J, Li J. RGS5, a hypoxia-inducible apoptotic stimulator in endothelial cells. J Biol Chem. 2009;284:23436-43 pubmed publisher..Moreover, RGS5 antagonizes the angiogenic effect of VEGF by increasing the activation of p38 signaling, suggesting that RGS5 could be an important target for apoptotic therapy. ..
- Cao Y, Pahlberg J, Sarria I, Kamasawa N, Sampath A, Martemyanov K. Regulators of G protein signaling RGS7 and RGS11 determine the onset of the light response in ON bipolar neurons. Proc Natl Acad Sci U S A. 2012;109:7905-10 pubmed publisher..These observations are consistent with persistently high G-protein activity in rod ON bipolar cell dendrites caused by the absence of the dominant GAP, biasing TRPM1 channels to the closed state. ..
- Anderson G, Posokhova E, Martemyanov K. The R7 RGS protein family: multi-subunit regulators of neuronal G protein signaling. Cell Biochem Biophys. 2009;54:33-46 pubmed publisher..The R7 group of RGS proteins (R7 RGS) has received special attention due to their pivotal roles in the regulation of a range of crucial ..
- Liang G, Bansal G, Xie Z, Druey K. RGS16 inhibits breast cancer cell growth by mitigating phosphatidylinositol 3-kinase signaling. J Biol Chem. 2009;284:21719-27 pubmed publisher..These results suggest that the loss of RGS16 in some breast tumors enhances PI3K signaling elicited by growth factors and thereby promotes proliferation and TKI evasion downstream of HER activation. ..
- Roman D, Blazer L, Monroy C, Neubig R. Allosteric inhibition of the regulator of G protein signaling-Galpha protein-protein interaction by CCG-4986. Mol Pharmacol. 2010;78:360-5 pubmed publisher..b>RGS proteins exert their effect by directly binding to the activated Galpha subunit of the G protein, catalyzing the ..
- James M, Lu Y, Liu Y, Vikis H, You M. RGS17, an overexpressed gene in human lung and prostate cancer, induces tumor cell proliferation through the cyclic AMP-PKA-CREB pathway. Cancer Res. 2009;69:2108-16 pubmed publisher..The prevalence of the induction of RGS17 in tumor tissues of various types further implicates its importance in the maintenance of tumor growth. ..
- Seredenina T, Gokce O, Luthi Carter R. Decreased striatal RGS2 expression is neuroprotective in Huntington's disease (HD) and exemplifies a compensatory aspect of HD-induced gene regulation. PLoS ONE. 2011;6:e22231 pubmed publisher..Our findings both identify RGS2 downregulation as a novel compensatory response in HD neurons and suggest that RGS2 inhibition might be considered as an innovative target for neuroprotective drug development. ..
- Sun Y, Fang R, Li C, Li L, Li F, Ye X, et al. Hsa-mir-182 suppresses lung tumorigenesis through down regulation of RGS17 expression in vitro. Biochem Biophys Res Commun. 2010;396:501-7 pubmed publisher..Taken together, these data have provided the first evidence of miRNA regulation of RGS17 expression in lung cancer. ..
- Zhang H, Gu S, Al Sabeq B, Wang S, He J, Tam A, et al. Origin-specific epigenetic program correlates with vascular bed-specific differences in Rgs5 expression. FASEB J. 2012;26:181-91 pubmed publisher..These data suggest that an origin-dependent epigenetic program regulates vascular bed- and maturation state-dependent regulation of VSMC-specific gene transcription. ..
- Zhang H, Tang W, Liu K, Huang Q, Zhang X, Yan X, et al. Eight RGS and RGS-like proteins orchestrate growth, differentiation, and pathogenicity of Magnaporthe oryzae. PLoS Pathog. 2011;7:e1002450 pubmed publisher..oryzae, MoRgs4 and other RGS and RGS-like proteins are also involved in a complex process governing asexual/sexual development, appressorium formation, and pathogenicity...
- Garzón J, Rodríguez Muñoz M, Vicente Sánchez A, Bailón C, Martinez Murillo R, Sánchez Blázquez P. RGSZ2 binds to the neural nitric oxide synthase PDZ domain to regulate mu-opioid receptor-mediated potentiation of the N-methyl-D-aspartate receptor-calmodulin-dependent protein kinase II pathway. Antioxid Redox Signal. 2011;15:873-87 pubmed publisher..This RGSZ2-dependent regulation of NMDAR activity is relevant to persistent pain disorders associated with heightened NMDAR-mediated glutamate responses and the reduced antinociceptive capacity of opioids. ..
- Tuomi J, Chidiac P, Jones D. Evidence for enhanced M3 muscarinic receptor function and sensitivity to atrial arrhythmia in the RGS2-deficient mouse. Am J Physiol Heart Circ Physiol. 2010;298:H554-61 pubmed publisher..01). These results suggest that RGS2 is an important cholinergic regulator in the atrium and that RGS2(-/-) mice have enhanced susceptibility to AT/F via enhanced M3 muscarinic receptor activity. ..
- Blazer L, Zhang H, Casey E, Husbands S, Neubig R. A nanomolar-potency small molecule inhibitor of regulator of G-protein signaling proteins. Biochemistry. 2011;50:3181-92 pubmed publisher..It has an IC(50) for RGS4 of 30 nM and is >20-fold selective for RGS4 over other RGS proteins. CCG-50014 binds covalently to the RGS, forming an adduct on two cysteine residues located in an allosteric ..
- Roman D, Ota S, Neubig R. Polyplexed flow cytometry protein interaction assay: a novel high-throughput screening paradigm for RGS protein inhibitors. J Biomol Screen. 2009;14:610-9 pubmed publisher..This report focuses on 5 RGS proteins (4, 6, 7, 8, and 16)...
- Hamel M, Dufort I, Robert C, Leveille M, Leader A, Sirard M. Genomic assessment of follicular marker genes as pregnancy predictors for human IVF. Mol Hum Reprod. 2010;16:87-96 pubmed publisher..These new approaches provide useful tools in the context of embryo selection and in the improvement of pregnancy rates with SET. ..