title: Functional role, mechanisms of regulation, and therapeutic potential of regulator of G protein signaling 2 in the heart.
abstract: G protein-mediated signal transduction is essential for the regulation of cardiovascular function, including heart rate, growth, contraction, and vascular tone. Regulators of G protein Signaling (RGS proteins) fine-tune G protein-coupled receptor-induced signaling by regulating its magnitude and duration through direct interaction with the α subunits of heterotrimeric G proteins. Changes in the RGS protein expression and/or function in the heart often lead to pathophysiological changes and are associated with cardiac disease in animals and humans, including hypertrophy, fibrosis development, heart failure, and arrhythmias. This article focuses on Regulator of G protein Signaling 2 (RGS2), which is widely expressed in many tissues and is highly regulated in its expression and function. Most information to date has been obtained in biochemical, cellular, and animal studies, but data from humans is emerging. We review recent advances on the functional role of cardiovascular RGS2 and the mechanisms that determine its signaling selectivity, expression, and functionality. We highlight key unanswered questions and discuss the potential of RGS2 as a therapeutic target.
authors: Cardiovascular Research Center, Cardiology Division, Rhode Island Hospital and Alpert Medical School of Brown University, Providence, RI, USA.
authors: Peng
authors: P
authors: Zhang
authors: Cardiovascular Research Center, Cardiology Division, Rhode Island Hospital and Alpert Medical School of Brown University, Providence, RI, USA. Electronic address: ulrike_mende@brown.edu.
authors: Ulrike
authors: U
authors: Mende
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D006801:Humans; D058990:Molecular Targeted Therapy; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D020710:RGS Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D020710:RGS Proteins; C087182:RGS2 protein, human
references: J Biol Chem. 2006 Oct 6;281(40):29669-74
references: 16895908
references: PLoS One. 2012;7(7):e40048
references: 22802950
references: J Biol Chem. 2011 Dec 30;286(52):44646-58
references: 22057271
references: Am J Physiol Heart Circ Physiol. 2011 Jul;301(1):H147-56
references: 21498776
references: Trends Biochem Sci. 2011 Sep;36(9):457-69
references: 21764321
references: Nucleic Acids Res. 2011 Jan;39(2):701-11
references: 20864449
references: Physiol Rev. 2005 Oct;85(4):1159-204
references: 16183910
references: Nature. 2001 Feb 22;409(6823):1051-5
references: 11234015
references: J Biol Chem. 2004 Feb 6;279(6):3906-15
references: 14630933
references: J Neurosci. 1998 Sep 15;18(18):7178-88
references: 9736641
references: J Am Soc Nephrol. 2010 Nov;21(11):1847-51
references: 20847141
references: J Biol Chem. 2006 Oct 27;281(43):32684-93
references: 16950788
references: Bone. 2002 May;30(5):677-84
references: 11996904
references: Am J Physiol Heart Circ Physiol. 2010 Feb;298(2):H554-61
references: 19966055
references: Clin Sci (Lond). 2009 Mar;116(5):391-9
references: 19175357
references: J Biol Chem. 2007 Nov 9;282(45):33064-75
references: 17848575
references: Pharmacol Rev. 2002 Sep;54(3):527-59
references: 12223533
references: Cell. 1996 Aug 9;86(3):445-52
references: 8756726
references: Proc Natl Acad Sci U S A. 2011 Dec 6;108(49):19713-8
references: 22080612
references: Circulation. 2009 Mar 10;119(9):1231-40
references: 19237665
references: Front Physiol. 2012 Apr 13;3:95
references: 22685433
references: Nature. 2013 Mar 28;495(7442):457-8
references: 23515157
references: J Biol Chem. 2001 Apr 27;276(17):14195-203
references: 11278586
references: Cell Signal. 2006 Dec;18(12):2182-92
references: 16820281
references: J Biol Chem. 2006 Mar 3;281(9):5811-20
references: 16380388
references: Mol Pharmacol. 2010 Oct;78(4):550-7
references: 20664002
references: Circ Res. 2011 Jul 22;109(3):320-33
references: 21778436
references: Front Physiol. 2012 Jun 29;3:239
references: 22754542
references: PLoS One. 2012;7(11):e46856
references: 23144791
references: Int J Biochem Cell Biol. 2006;38(12):2209-18
references: 16945566
references: Nat Rev Mol Cell Biol. 2013 Jan;14(1):38-48
references: 23258295
references: Mol Pharmacol. 2000 Mar;57(3):460-7
references: 10692485
references: Am J Physiol Heart Circ Physiol. 2012 Jul;303(1):H19-35
references: 22542620
references: Basic Res Cardiol. 2010 Sep;105(5):583-95
references: 20352235
references: Pharmacol Ther. 2007 Dec;116(3):473-95
references: 18006065
references: Mol Pharmacol. 2012 Sep;82(3):500-9
references: 22695717
references: Nat Cell Biol. 2005 Apr;7(4):405-11
references: 15793568
references: Structure. 2013 Mar 5;21(3):438-48
references: 23434405
references: Eur J Pharmacol. 2008 May 13;585(2-3):278-91
references: 18410914
references: Trends Cardiovasc Med. 2013 Oct;23(7):242-9
references: 23499300
references: Cell Signal. 2006 Oct;18(10):1655-63
references: 16517124
references: Int J Cancer. 2012 Apr 1;130(7):1521-31
references: 21500190
references: Cell Signal. 2010 Sep;22(9):1274-81
references: 20363320
references: Semin Cell Dev Biol. 2006 Jun;17(3):383-9
references: 16647283
references: Mol Pharmacol. 2007 Apr;71(4):1040-50
references: 17220356
references: J Clin Invest. 2003 Feb;111(4):445-52
references: 12588882
references: J Physiol. 2012 Mar 15;590(6):1313-30
references: 22183719
references: Nat Rev Cardiol. 2011 Dec 06;9(3):147-57
references: 22143079
references: Circ Res. 2008 Oct 24;103(9):919-28
references: 18948630
references: Proc Natl Acad Sci U S A. 1997 Dec 23;94(26):14389-93
references: 9405622
references: J Biol Chem. 2001 Feb 23;276(8):5438-44
references: 11063746
references: J Hypertens. 2005 Aug;23(8):1497-505
references: 16003176
references: J Cell Biol. 2009 Sep 7;186(5):755-65
references: 19736320
references: Nat Med. 2003 Dec;9(12):1506-12
references: 14608379
references: Biol Psychiatry. 2011 Mar 15;69(6):526-33
references: 21168126
references: Heart Rhythm. 2009 Jan;6(1):85-6
references: 19121806
references: J Biol Chem. 2004 May 14;279(20):21248-56
references: 14976183
references: Proc Natl Acad Sci U S A. 1997 Jan 21;94(2):428-32
references: 9012799
references: J Clin Invest. 2009 Feb;119(2):408-20
references: 19127022
references: J Mol Cell Cardiol. 2006 Jul;41(1):51-61
references: 16756988
references: Prog Mol Biol Transl Sci. 2010;91:81-119
references: 20691960
references: J Biol Chem. 2007 Oct 26;282(43):31656-65
references: 17681944
references: Mol Pharmacol. 2005 Mar;67(3):631-9
references: 15563583
references: Mol Pharmacol. 2008 Apr;73(4):1037-43
references: 18230714
references: J Biol Chem. 2012 Apr 6;287(15):12541-9
references: 22354966
references: Sci Transl Med. 2011 Sep 14;3(100):100ra88
references: 21918105
references: Mol Biol Cell. 2000 Sep;11(9):3155-68
references: 10982407
references: J Biol Chem. 2003 May 2;278(18):15842-9
references: 12604604
references: J Mol Cell Cardiol. 2011 Jun;50(6):1000-7
references: 21291891
references: Mol Pharmacol. 2008 Jan;73(1):1-11
references: 17901199