RGS2

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Regulator of G-protein signaling 2
Protein RGS2 PDB 2af0.png
PDB rendering based on 2af0.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols RGS2 ; G0S8
External IDs OMIM600861 MGI1098271 HomoloGene2192 GeneCards: RGS2 Gene
RNA expression pattern
PBB GE RGS2 202388 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 5997 19735
Ensembl ENSG00000116741 ENSMUSG00000026360
UniProt P41220 O08849
RefSeq (mRNA) NM_002923 NM_009061
RefSeq (protein) NP_002914 NP_033087
Location (UCSC) Chr 1:
192.78 – 192.78 Mb
Chr 1:
144 – 144 Mb
PubMed search [1] [2]

Regulator of G-protein signaling 2 is a protein that in humans is encoded by the RGS2 gene.[1][2] It is part of a larger family of RGS proteins that control signalling through G-protein coupled receptors (GPCR).

Function[edit]

RGS2 is thought to have protective effects against myocardial hypertrophy as well as atrial arrhythmias.[3][4] Increased stimulation of Gs coupled β1-adrenergic receptors and Gq coupled α1-adrenergic receptors in the heart can result in cardiac hypertrophy.[3] In the case of Gq protein coupled receptor (GqPCR) mediated hypertrophy, Gαq will activate the intracellular affectors phospholipase Cβ and rho guanine nucleotide exhange factor to stimulate cell processes which lead to cardiomyocyte hypertrophy.[3][5] RGS2 functions as a GTPase Activating Protein (GAP) which acts to increase the natural GTPase activity of the Gα subunit.[3][5] By increasing the GTPase activity of the Gα subunit, RGS2 promotes GTP hydrolysis back to GDP, thus converting the Gα subunit back to its inactive state and reducing its signalling ability.[5] Both GsPCR and GqPCR activation can contribute to cardiac hypertrophy via activation of MAP Kinases as well. RGS2 has been shown to decrease phosphorylation of those MAP kinases and therefore decrease their activation in response to Gαs signalling.[3]

In the case of GsPCR mediated hypertrophy, the main mechanism by which signalling contributes to hypertrophy is through the Gβγ subunit; Gαs signalling by itself is not sufficient.[6] Nevertheless, RGS2 has been shown to inhibit Gs mediated hypertrophy. The mechanism of how RGS2 regulates increased Gβγ signalling is not well understood, apart from the fact that it is unrelated to RGS2’s GAP function.[6] A deficiency in RGS2 has been linked with increased cardiac hypertrophy in mice.[3] RGS2 deficient hearts appear normal until confronted with an increased workload, to which they respond readily with increased Gαq signalling and hypertrophy.[3][6]

Gαs subunits increase adenyl cyclase activity, which in turn leads to cAMP accumulation in the myocyte nucleus to trigger hypertrophy. RGS2 regulates the effects of increased Gαs signalling through its GAP function.[3] Stimulation of GsPCRs not only leads to hypertrophy but it has also been shown to selectively induce higher expression levels of RGS2 which in turn, protects against hypertrophy, providing a mechanism for maintaining homeostatic conditions.[3]

There has also been some evidence of a role of RGS2 in atrial arrhythmias where RGS2 deficient mice exhibited prolonged and greater susceptibility to electrically induced atrial fibrillation.[4] This was attributed to a decrease in RGS2’s inhibitory effects on Gq coupled M3 muscarinic receptor signalling, resulting in increased Gαq activity.[4] The M3 muscarinic receptor normally activates delayed rectifier potassium channels in the atria, thus increased Gαq activity is thought to result in an altered potassium flux, a decreased refractory period, increased chance of current re-entry and inappropriate contraction.[4]

[7] [8]

Interactions[edit]

RGS2 has been shown to interact with PRKG1[9] and ADCY5.[10]

References[edit]

  1. ^ Siderovski DP, Heximer SP, Forsdyke DR (Jun 1994). "A human gene encoding a putative basic helix-loop-helix phosphoprotein whose mRNA increases rapidly in cycloheximide-treated blood mononuclear cells". DNA Cell Biol 13 (2): 125–47. doi:10.1089/dna.1994.13.125. PMID 8179820. 
  2. ^ "RGS2 regulator of G-protein signaling 2, 24kDa". 
  3. ^ a b c d e f g h i Nunn C, Zou MX, Sobiesiak AJ, Roy AA, Kirshenbaum LA, Chidiac P (August 2010). "RGS2 inhibits beta-adrenergic receptor-induced cardiomyocyte hypertrophy". Cell. Signal. 22 (8): 1231–9. doi:10.1016/j.cellsig.2010.03.015. PMID 20362664. 
  4. ^ a b c d Tuomi JM, Chidiac P, Jones DL (February 2010). "Evidence for enhanced M3 muscarinic receptor function and sensitivity to atrial arrhythmia in the RGS2-deficient mouse". Am. J. Physiol. Heart Circ. Physiol. 298 (2): H554–61. doi:10.1152/ajpheart.00779.2009. PMID 19966055. 
  5. ^ a b c Park-Windhol C, Zhang P, Zhu M, Su J, Chaves L, Maldonado AE, King ME, Rickey L, Cullen D, Mende U (2012). "Gq/11-mediated signaling and hypertrophy in mice with cardiac-specific transgenic expression of regulator of G-protein signaling 2". PLoS ONE 7 (7): e40048. doi:10.1371/journal.pone.0040048. PMC 3388988. PMID 22802950. 
  6. ^ a b c Vidal M, Wieland T, Lohse MJ, Lorenz K (November 2012). "β-Adrenergic receptor stimulation causes cardiac hypertrophy via a Gβγ/Erk-dependent pathway". Cardiovasc. Res. 96 (2): 255–64. doi:10.1093/cvr/cvs249. PMID 22843704. 
  7. ^ Wieland T, Lutz S, Chidiac P (April 2007). "Regulators of G protein signalling: a spotlight on emerging functions in the cardiovascular system". Curr Opin Pharmacol 7 (2): 201–7. doi:10.1016/j.coph.2006.11.007. PMID 17276730. 
  8. ^ Tsang S, Woo AY, Zhu W, Xiao RP (2010). "Deregulation of RGS2 in cardiovascular diseases". Front Biosci (Schol Ed) 2: 547–57. PMC 2815333. PMID 20036967. 
  9. ^ Tang KM, Wang GR, Lu P, Karas RH, Aronovitz M, Heximer SP, Kaltenbronn KM, Blumer KJ, Siderovski DP, Zhu Y, Mendelsohn ME, Tang M, Wang G (December 2003). "Regulator of G-protein signaling-2 mediates vascular smooth muscle relaxation and blood pressure". Nat. Med. 9 (12): 1506–12. doi:10.1038/nm958. PMID 14608379. 
  10. ^ Salim S, Sinnarajah S, Kehrl JH, Dessauer CW (May 2003). "Identification of RGS2 and type V adenylyl cyclase interaction sites". J. Biol. Chem. 278 (18): 15842–9. doi:10.1074/jbc.M210663200. PMID 12604604. 

Further reading[edit]