Historical Background
The regulator of G protein signaling 10 (RGS10) protein is a regulatory molecule that belongs to a larger family of RGS proteins responsible for altering cellular signaling. Generally, RGS proteins are negative regulators of signal transduction pathways mediated by heterotrimeric G proteins. This function allows RGS proteins to control the duration and amplification of signaling activity, ultimately operating as shut-off switches. RGS proteins deactivate G protein subunits by serving as GTPase activating proteins (GAPs), which enhance the intrinsic GTPase activity of the active, GTP-bound Gα subunit and return G proteins to their inactive, GDP-bound form. The result is an acceleration of the deactivation of G protein signaling.
Protein Structure and Function
All RGS proteins share a conserved 120 amino acid helical RGS domain that is responsible for GAP activity. Based on sequence similarity of the RGS domain, RGS10 is grouped in the RGS 12 subfamily which also...
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Ahmadian MR, Stege P, Scheffzek K, Wittinghofer A. Confirmation of the arginine-finger hypothesis for the GAP-stimulated GTP-hydrolysis reaction of Ras. Nat Struct Biol. 1997;4:686–9.
Alexander SPH, Kelly E, Marrion N, Peters JA, Benson HE, Faccenda E, et al. The concise guide to pharmacology 2015/16: overview. Br J Pharmacol. 2015;172:5729–43.
Ali MW, Cacan E, Liu Y, Pierce JY, Creasman WT, Murph MM, et al. Transcriptional suppression, DNA methylation, and histone deacetylation of the regulator of G-protein signaling 10 (RGS10) gene in ovarian cancer cells. PLoS One. 2013;8:e60185. https://doi.org/10.1371/journal.pone.0060185.
Altman MK, Alshamrani AA, Jia W, Nguyen HT, Fambrough JM, Tran SK, et al. Suppression of the GTPase-activating protein RGS10 increases Rheb-GTP and mTOR signaling in ovarian cancer cells. Cancer Lett. 2015;369:175–83. https://doi.org/10.1016/j.canlet.2015.08.012.
Burgon PG, Lee WL, Nixon AB, Peralta EG, Casey PJ. Phosphorylation and nuclear translocation of a regulator of G protein signaling (RGS10). J Biol Chem. 2001;276:32828–34. https://doi.org/10.1074/jbc.M100960200.
Cacan E, Ali MW, Boyd NH, Hooks SB, Greer SF. Inhibition of HDAC1 and DNMT1 modulate RGS10 expression and decrease ovarian cancer chemoresistance. PLoS One. 2014;9:e87455. https://doi.org/10.1371/journal.pone.0087455.
Chatterjee TK, Fisher RA. Cytoplasmic, nuclear, and golgi localization of RGS proteins. Evidence for N-terminal and RGS domain sequences as intracellular targeting motifs. J Biol Chem. 2000;275:24013–21. https://doi.org/10.1074/jbc.M002082200.
Haller C, Fillatreau S, Hoffmann R, Agenes F. Structure, chromosomal localization and expression of the mouse regulator of G-protein signaling10 gene (mRGS10). Gene. 2002;297:39–49.
Hensch NR, Karim ZA, Druey KM, Tansey MG, Khasawneh FT. RGS10 negatively regulates platelet activation and thrombogenesis. PLoS One. 2016;11:e0165984. https://doi.org/10.1371/journal.pone.0165984.
Hollinger S, Hepler JR. Cellular regulation of RGS proteins: modulators and integrators of G protein signaling. Pharmacol Rev. 2002;54:527–59.
Hooks SB, Callihan P, Altman MK, Hurst JH, Ali MW, Murph MM. Regulators of G-protein signaling RGS10 and RGS17 regulate chemoresistance in ovarian cancer cells. Mol Cancer. 2010;9:289. https://doi.org/10.1186/1476-4598-9-289.
Hunt TW, Fields TA, Casey PJ, Peralta EG. RGS10 is a selective activator of G alpha i GTPase activity. Nature. 1996;383:175–7. https://doi.org/10.1038/383175a0.
Kannarkat GT, Lee JK, Ramsey CP, Chung J, Chang J, Porter I, et al. Age-related changes in regulator of G-protein signaling (RGS)-10 expression in peripheral and central immune cells may influence the risk for age-related degeneration. Neurobiol Aging. 2015;36:1982–93. https://doi.org/10.1016/j.neurobiolaging.2015.02.006.
Lee JK, Tansey MG. Physiology of RGS10 in neurons and immune cells. Prog Mol Biol Transl Sci. 2015;133:153–67. https://doi.org/10.1016/bs.pmbts.2015.01.005.
Lee JK, McCoy MK, Harms AS, Ruhn KA, Gold SJ, Tansey MG. Regulator of G-protein signaling 10 promotes dopaminergic neuron survival via regulation of the microglial inflammatory response. J Neurosci Off J Soc Neurosci. 2008;28:8517–28. https://doi.org/10.1523/JNEUROSCI.1806-08.2008.
Lee JK, Chung J, McAlpine FE, Tansey MG. Regulator of G-protein signaling-10 negatively regulates NF-kappaB in microglia and neuroprotects dopaminergic neurons in hemiparkinsonian rats. J Neurosci Off J Soc Neurosci. 2011;31:11879–88. https://doi.org/10.1523/JNEUROSCI.1002-11.2011.
Lee JK, Chung J, Druey KM, Tansey MG. RGS10 exerts a neuroprotective role through the PKA/c-AMP response-element (CREB) pathway in dopaminergic neuron-like cells. J Neurochem. 2012;122:333–43. https://doi.org/10.1111/j.1471-4159.2012.07780.x.
Lee JK, Chung J, Kannarkat GT, Tansey MG. Critical role of regulator G-protein signaling 10 (RGS10) in modulating macrophage M1/M2 activation. PLoS One. 2013;8:e81785. https://doi.org/10.1371/journal.pone.0081785.
Lee JK, Kannarkat GT, Chung J, Joon Lee H, Graham KL, Tansey MG. RGS10 deficiency ameliorates the severity of disease in experimental autoimmune encephalomyelitis. J Neuroinflammation. 2016;13:24. https://doi.org/10.1186/s12974-016-0491-0.
Li Y, Inoki K, Guan KL. Biochemical and functional characterizations of small GTPase Rheb and TSC2 GAP activity. Mol Cell Biol. 2004;24:7965–75. https://doi.org/10.1128/MCB.24.18.7965-7975.2004.
Ma P, Cierniewska A, Signarvic R, Cieslak M, Kong H, Sinnamon AJ, et al. A newly identified complex of spinophilin and the tyrosine phosphatase, SHP-1, modulates platelet activation by regulating G protein-dependent signaling. Blood. 2012;119:1935–45. https://doi.org/10.1182/blood-2011-10-387910.
Miao R, Lu Y, Xing X, Li Y, Huang Z, Zhong H, et al. Regulator of G-protein signaling 10 negatively regulates cardiac remodeling by blocking mitogen-activated protein kinase-extracellular signal-regulated protein kinase 1/2 signaling. Hypertension. 2016;67:86–98. https://doi.org/10.1161/HYPERTENSIONAHA.115.05957.
Popov S, Yu K, Kozasa T, Wilkie TM. The regulators of G protein signaling (RGS) domains of RGS4, RGS10, and GAIP retain GTPase activating protein activity in vitro. Proc Natl Acad Sci USA. 1997;94:7216–20.
Soundararajan M, Willard FS, Kimple AJ, Turnbull AP, Ball LJ, Schoch GA, et al. Structural diversity in the RGS domain and its interaction with heterotrimeric G protein alpha-subunits. Proc Natl Acad Sci USA. 2008;105:6457–62. https://doi.org/10.1073/pnas.0801508105.
Taylor VG, Bommarito PA, Tesmer JJ. Structure of the regulator of G protein signaling 8 (RGS8)-Galphaq complex: molecular basis for Galpha selectivity. J Biol Chem. 2016;291:5138–45. https://doi.org/10.1074/jbc.M115.712075.
Tu Y, Wang J, Ross EM. Inhibition of brain Gz GAP and other RGS proteins by palmitoylation of G protein alpha subunits. Science. 1997;278:1132–5.
Tu Y, Popov S, Slaughter C, Ross EM. Palmitoylation of a conserved cysteine in the regulator of G protein signaling (RGS) domain modulates the GTPase-activating activity of RGS4 and RGS10. J Biol Chem. 1999;274:38260–7.
Tuggle K, Ali MW, Salazar H, Hooks SB. Regulator of G protein signaling transcript expression in human neural progenitor differentiation: R7 subfamily regulation by DNA methylation. Neurosignals. 2014;22:43–51. https://doi.org/10.1159/000362128.
Watson N, Linder ME, Druey KM, Kehrl JH, Blumer KJ. RGS family members: GTPase-activating proteins for heterotrimeric G-protein alpha-subunits. Nature. 1996;383:172–5. https://doi.org/10.1038/383172a0.
Wen L, Li J, Guo H, Liu X, Zheng S, Zhang D, et al. Genome-scale detection of hypermethylated CpG islands in circulating cell-free DNA of hepatocellular carcinoma patients. Cell Res. 2015;25:1250–64. https://doi.org/10.1038/cr.2015.126.
Yang S, Li YP. RGS10-null mutation impairs osteoclast differentiation resulting from the loss of [Ca2+]i oscillation regulation. Genes Dev. 2007;21:1803–16. https://doi.org/10.1101/gad.1544107.
Yang S, Chen W, Stashenko P, Li YP. Specificity of RGS10A as a key component in the RANKL signaling mechanism for osteoclast differentiation. J Cell Sci. 2007;120:3362–71. https://doi.org/10.1242/jcs.008300.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer International Publishing AG
About this entry
Cite this entry
Hooks, S.B., Murph, M.M. (2018). RGS10. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_101851
Download citation
DOI: https://doi.org/10.1007/978-3-319-67199-4_101851
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-67198-7
Online ISBN: 978-3-319-67199-4
eBook Packages: Biomedical and Life SciencesReference Module Biomedical and Life Sciences