A peptide of the RGS domain of GRK2 binds and inhibits Gαq to suppress pathological cardiac hypertrophy and dysfunction

Science Signaling

Volumn 9, Issue 420, 2016, Pages

  Schumacher, Sarah M ^a   Gao, Erhe ^a   Cohen, Maya ^a   Lieu, Melissa ^a   Chuprun, J Kurt ^a   Koch, Walter J ^a  

^a TEMPLE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BETA ADRENERGIC RECEPTOR KINASE; BETA ADRENERGIC RECEPTOR KINASE RGS PEPTIDE; G PROTEIN COUPLED RECEPTOR KINASE 2; GUANINE NUCLEOTIDE BINDING PROTEIN; RGS PROTEIN; UNCLASSIFIED DRUG; ADRBK1 PROTEIN, MOUSE; GUANINE NUCLEOTIDE BINDING PROTEIN ALPHA SUBUNIT; PEPTIDE; PROTEIN BINDING;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; GENE EXPRESSION; HEART DISEASE; HEART FAILURE; HEART FUNCTION; HEART LEFT VENTRICLE HYPERTROPHY; HEART LEFT VENTRICLE OVERLOAD; HEART VENTRICLE HYPERTROPHY; HEART VENTRICLE REMODELING; MOUSE; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN PROTEIN INTERACTION; SIGNAL TRANSDUCTION; ANIMAL; CARDIOMEGALY; ENZYMOLOGY; GENETICS; METABOLISM; PATHOLOGY; PATHOPHYSIOLOGY; TRANSGENIC MOUSE;

ANIMALS; CARDIOMEGALY; G-PROTEIN-COUPLED RECEPTOR KINASE 2; GTP-BINDING PROTEIN ALPHA SUBUNITS, GQ-G11; HEART FAILURE; MICE; MICE, TRANSGENIC; PEPTIDES; PROTEIN BINDING; PROTEIN DOMAINS;

EID: 84961839547     PISSN: 19450877     EISSN: 19379145     Source Type: Journal    
DOI: 10.1126/scisignal.aae0549     Document Type: Article

References (45)

1. R. B. Penn, A. N. Pronin, J. L. Benovic, Regulation of G protein-coupled receptor kinases. Trends Cardiovasc. Med. 10, 81-89 (2000).
2. K. L. Pierce, R. T. Premont, R. J. Lefkowitz, Seven-transmembrane receptors. Nat. Rev. Mol. Cell Biol. 3, 639-650 (2002).
3. P. Y. Sato, J. K. Chuprun, M. Schwartz, W. J. Koch, The evolving impact of G proteincoupled receptor kinases in cardiac health and disease. Physiol. Rev. 95, 377-404 (2015).
4. T. Evron, T. L. Daigle, M. G. Caron, GRK2: Multiple roles beyond G protein-coupled receptor desensitization. Trends Pharmacol. Sci. 33, 154-164 (2012).
5. P. Penela, C. Murga, C. Ribas, V. Lafarga, F. Mayor Jr., The complex G proteincoupled receptor kinase 2 (GRK2) interactome unveils new physiopathological targets. Br. J. Pharmacol. 160, 821-832 (2010).
6. C. V. Carman, J.-L. Parent, P. W. Day, A. N. Pronin, P. M. Sternweis, P. B. Wedegaertner, A. G. Gilman, J.-L. Benovic, T. Kozasa, Selective regulation of Gaq/11 by an RGS domain in the G protein-coupled receptor kinase, GRK2. J. Biol. Chem. 274, 34483-34492 (1999).
7. M. Sallese, S. Mariggio, E. D'Urbano, L. Iacovelli, A. De Blasi, Selective regulation of Gq signaling by G protein-coupled receptor kinase 2: Direct interaction of kinase N terminus with activated Gaq. Mol. Pharmacol. 57, 826-831 (2000).
8. R. Sterne-Marr, J. J.G. Tesmer, P.W. Day, R. P. Stracquatanio, J.-A. E. Cilente, K. E. O'Connor, A. N. Pronin, J. L. Benovic, P. B. Wedegaertner, G protein-coupled receptor Kinase 2/Gaq/11 interaction. A novel surface on a regulator of G protein signaling homology domain for binding G alpha subunits. J. Biol. Chem. 278, 6050-6058 (2003).
9. H. Usui, M. Nishiyama, K. Moroi, T. Shibasaki, J. Zhou, J. Ishida, A. Fukamizu, T. Haga, S. Sekiya, S. Kimura, RGS domain in the amino-terminus of G protein-coupled receptor kinase 2 inhibits Gq-mediated signaling. Int. J. Mol. Med. 5, 335-340 (2000).
10. J. H. Rogers, A. Tsirka, A. Kovacs, K. J. Blumer, G. W. Dorn II, A. J. Muslin, RGS4 reduces contractile dysfunction and hypertrophic gene induction in Gaq overexpressing mice. J. Mol. Cell. Cardiol. 33, 209-218 (2001).
11. R. Sterne-Marr, G. K. Dhami, J. J. G. Tesmer, S. S. G. Ferguson, Characterization of GRK2 RH domain-dependent regulation of GPCR coupling to heterotrimeric G proteins. Methods Enzymol. 390, 310-336 (2004).
12. G. K. Dhami, P. H. Anborgh, L. B. Dale, R. Sterne-Marr, S. S. G. Ferguson, Phosphorylationindependent regulation of metabotropic glutamate receptor signaling by G protein-coupled receptor kinase 2. J. Biol. Chem. 277, 25266-25272 (2002).
13. P. W. Day, J. J. G. Tesmer, R. Sterne-Marr, L. C. Freeman, J. L. Benovic, P. B.Wedegaertner, Characterization of the GRK2 binding site of Gaq. J. Biol. Chem. 279, 53643-53652 (2004).
14. G. W. Dorn II, T. Force, Protein kinase cascades in the regulation of cardiac hypertrophy. J. Clin. Invest. 115, 527-537 (2005).
15. W. Nadruz, Myocardial remodeling in hypertension. J. Hum. Hypertens. 29, 1-6 (2015).
16. B. H. Lorell, B. A. Carabello, Left ventricular hypertrophy: Pathogenesis, detection, and prognosis. Circulation 102, 470-479 (2000).
17. M. H. Drazner, The progression of hypertensive heart disease. Circulation 123, 327-334 (2011).
18. D. D. D'Angelo, Y. Sakata, J. N. Lorenz, G. P. Boivin, R. A.Walsh, S. B. Liggett, G. W. Dorn II, Transgenic Gaq overexpression induces cardiac contractile failure in mice. Proc. Natl. Acad. Sci. U.S.A. 94, 8121-8126 (1997).
19. G. W. Dorn II, N. M. Tepe, J. N. Lorenz, W. J. Koch, S. B. Liggett, Low- and high-level transgenic expression of b2-adrenergic receptors differentially affect cardiac hypertrophy and function in Gaq-overexpressing mice. Proc. Natl. Acad. Sci. U.S.A. 96, 6400-6405 (1999).
20. J.W.Adams, Y.Sakata, M.G.Davis, V.P.Sah, Y.Wang, S.B. Liggett, K.R. Chien, J. H.Brown, G. W.Dorn II, EnhancedGaq signaling: A common pathway mediates cardiac hypertrophy and apoptotic heart failure. Proc. Natl. Acad. Sci. U.S.A. 95, 10140-10145 (1998).
21. S. A. Akhter, L. M. Luttrell, H. A. Rockman, G. Iaccarino, R. J. Lefkowitz, W. J. Koch, Targeting the receptor-Gq interface to inhibit in vivo pressure overload myocardial hypertrophy. Science 280, 574-577 (1998).
22. G. Esposito, S. V. Naga Prasad, A. Rapacciuolo, L. Mao, W. J. Koch, H. A. Rockman, Cardiac overexpression of a Gq inhibitor blocks induction of extracellular signal-regulated kinase and c-Jun NH2-terminal kinase activity in in vivo pressure overload. Circulation 103, 1453-1458 (2001).
23. G. Esposito, A. Rapacciuolo, S. V. Naga Prasad, H. Takaoka, S. A. Thomas, W. J. Koch, H. A. Rockman, Genetic alterations that inhibit in vivo pressure-overload hypertrophy prevent cardiac dysfunction despite increased wall stress. Circulation 105, 85-92 (2002).
24. J. S. Martini, P. Raake, L. E. Vinge, B. R. DeGeorge Jr., J. K. Chuprun, D. M. Harris, E. Gao, A. D. Eckhart, J. A. Pitcher, W. J. Koch, Uncovering G protein-coupled receptor kinase-5 as a histone deacetylase kinase in the nucleus of cardiomyocytes. Proc. Natl. Acad. Sci. U.S.A. 105, 12457-12462 (2008).
25. W. J. Koch, H. A. Rockman, P. Samama, R. A. Hamilton, R. A. Bond, C. A. Milano, R. J. Lefkowitz, Cardiac function in mice overexpressing the b-adrenergic receptor kinase or a bARK inhibitor. Science 268, 1350-1353 (1995).
26. H. A. Rockman, K. R. Chien, D.-J. Choi, G. Iaccarino, J. J. Hunter, J. Ross Jr., R. J. Lefkowitz, W. J. Koch, Expression of a b-adrenergic receptor kinase 1 inhibitor prevents the development of myocardial failure in gene-targeted mice. Proc. Natl. Acad. Sci. U.S.A. 95, 7000-7005 (1998).
27. H. Brinks, M. Boucher, E. Gao, J. K. Chuprun, S. Pesant, P. W. Raake, Z. M. Huang, X. Wang, G. Qiu, A. Gumpert, D. M. Harris, A. D. Eckhart, P. Most, W. J. Koch, Level of G protein-coupled receptor kinase-2 determines myocardial ischemia/reperfusion injury via pro- and anti-apoptotic mechanisms. Circ. Res. 107, 1140-1149 (2010).
28. M. Chen, P. Y. Sato, J. K. Chuprun, R. J. Peroutka, N. J. Otis, J. Ibetti, S. Pan, S.-S. Sheu, E. Gao, W. J. Koch, Prodeath signaling of G protein-coupled receptor kinase 2 in cardiac myocytes after ischemic stress occurs via extracellular signal-regulated kinase-dependent heat shock protein 90-mediated mitochondrial targeting. Circ. Res. 112, 1121-1134 (2013).
29. Q. Fan, M. Chen, L. Zuo, X. Shang, M. Z. Huang, M. Ciccarelli, P. Raake, H. Brinks, K. J. Chuprun, G. W. Dorn II, W. J. Koch, E. Gao, Myocardial ablation of G protein-coupled receptor kinase 2 (GRK2) decreases ischemia/reperfusion injury through an anti-intrinsic apoptotic pathway. PLOS One 8, e66234 (2013).
30. V. M. Tesmer, T. Kawano, A. Shankaranarayanan, T. Kozasa, J. J. G. Tesmer, Snapshot of activated G proteins at the membrane: The Gaq-GRK2-Gbg complex. Science 310, 1686-1690 (2005).
31. A. M. Lyon, V. G. Taylor, J. J. G. Tesmer, Strike a pose: Gaq complexes at the membrane. Trends Pharmacol. Sci. 35, 23-30 (2014).
32. C. V. Carman, M. P. Lisanti, J. L. Benovic, Regulation of G protein-coupled receptor kinases by caveolin. J. Biol. Chem. 274, 8858-8864 (1999).
33. A. N. Pronin, D. K. Satpaev, V. Z. Slepak, J. L. Benovic, Regulation of G proteincoupled receptor kinases by calmodulin and localization of the calmodulin binding domain. J. Biol. Chem. 272, 18273-18280 (1997).
34. S. Mariggiò, C. García-Hoz, S. Sarnago, A. De Blasi, F. Mayor Jr., C. Ribas, Tyrosine phosphorylation of G-protein-coupled-receptor kinase 2 (GRK2) by c-Src modulates its interaction with Gaq. Cell. Signal. 18, 2004-2012 (2006).
35. B. C. Bernardo, K. L. Weeks, L. Pretorius, J. R. McMullen, Molecular distinction between physiological and pathological cardiac hypertrophy: Experimental findings and therapeutic strategies. Pharmacol. Ther. 128, 191-227 (2010).
36. J. R. McMullen, G. L. Jennings, Differences between pathological and physiological cardiac hypertrophy: Novel therapeutic strategies to treat heart failure. Clin. Exp. Pharmacol. Physiol. 34, 255-262 (2007).
37. P. W. J. Raake, P. Schlegel, J. Ksienzyk, J. Reinkober, J. Barthelmes, S. Schinkel, S. Pleger, W. Mier, U. Haberkorn, W. J. Koch, H. A. Katus, P. Most, O. J. Müller, AAV6.bARKct cardiac gene therapy ameliorates cardiac function and normalizes the catecholaminergic axis in a clinically relevant large animal heart failure model. Eur. Heart J. 34, 1437-1447 (2013).
38. G. Rengo, A. Lymperopoulos, C. Zincarelli, M. Donniacuo, S. Soltys, J. E. Rabinowitz, W. J. Koch, Myocardial adeno-associated virus serotype 6-bARKct gene therapy improves cardiac function and normalizes the neurohormonal axis in chronic heart failure. Circulation 119, 89-98 (2009).
39. S. L. Ginn, I. E. Alexander, M. L. Edelstein, M. R. Abedi, J. Wixon, Gene therapy clinical trials worldwide to 2012-An update. J. Gene Med. 15, 65-77 (2013).
40. L. M. Casey, A. R. Pistner, S. L. Belmonte, D. Migdalovich, O. Stolpnik, F. E. Nwakanma, G. Vorobiof, O. Dunaevsky, A. Matavel, C. M. B. Lopes, A. V. Smrcka, B. C. Blaxall, Small molecule disruption of Gbg signaling inhibits the progression of heart failure. Circ. Res. 107, 532-539 (2010).
41. F. A. Kamal, D. M. Mickelsen, K. M. Wegman, J. G. Travers, J. Moalem, S. R. Hammes, A. V. Smrcka, B. C. Blaxall, Simultaneous adrenal and cardiac G-protein-coupled receptor- Gbg inhibition halts heart failure progression. J. Am. Coll. Cardiol. 63, 2549-2557 (2014).
42. T. J. Rettenmaier, J. D. Sadowsky, N. D. Thomsen, S. C. Chen, A. K. Doak, M. R. Arkin, J. A. Wells, A small-molecule mimic of a peptide docking motif inhibits the protein kinase PDK1. Proc. Natl. Acad. Sci. U.S.A. 111, 18590-18595 (2014).
43. J. R. Keys, E. A. Greene, C. J. Cooper, S. V. Naga Prasad, H. A. Rockman, W. J. Koch, Cardiac hypertrophy and altered b-adrenergic signaling in transgenic mice that express the amino terminus of b-ARK1. Am. J. Physiol. Heart Circ. Physiol. 285, H2201-H2211 (2003).
44. E. Gao, Y. H. Lei, X. Shang, Z. M. Huang, L. Zuo, M. Boucher, Q. Fan, J. K. Chuprun, X. L. Ma, W. J. Koch, A novel and efficient model of coronary artery ligation and myocardial infarction in the mouse. Circ. Res. 107, 1445-1453 (2010).
45. Z. M. Huang, E. Gao, F. V. Fonseca, H. Hayashi, X. Shang, N. E. Hoffman, J. K. Chuprun, X. Tian, D. G. Tilley, M. Madesh, D. J. Lefer, J. S. Stamler, W. J. Koch, Convergence of G protein-coupled receptor and S-nitrosylation signaling determines the outcome to cardiac ischemic injury. Sci. Signal. 6, ra95 (2013).