{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:37:35Z","timestamp":1790836655181,"version":"4.1.0"},"reference-count":39,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2017,7,31]],"date-time":"2017-07-31T00:00:00Z","timestamp":1501459200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["RA 1668\/6-1"],"award-info":[{"award-number":["RA 1668\/6-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["RA 1668\/3-1"],"award-info":[{"award-number":["RA 1668\/3-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["RA 1668\/1-1"],"award-info":[{"award-number":["RA 1668\/1-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005971","name":"Deutsche Herzstiftung","doi-asserted-by":"publisher","award":["F\/43\/13"],"award-info":[{"award-number":["F\/43\/13"]}],"id":[{"id":"10.13039\/501100005971","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004784","name":"Novartis Stiftung\u00a0f\u00fcr\u00a0Medizinisch-Biologische Forschung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004784","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0182110","type":"journal-article","created":{"date-parts":[[2017,7,31]],"date-time":"2017-07-31T20:28:29Z","timestamp":1501532909000},"page":"e0182110","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":41,"title":["G protein-coupled receptor kinase 2 promotes cardiac hypertrophy"],"prefix":"10.1371","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8365-674X","authenticated-orcid":true,"given":"Philipp","family":"Schlegel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Reinkober","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Meinhardt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrike","family":"Tscheschner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erhe","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah M.","family":"Schumacher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ancai","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Backs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Most","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Wieland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter J.","family":"Koch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugo A.","family":"Katus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip W.","family":"Raake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2017,7,31]]},"reference":[{"issue":"3","key":"ref1","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/S0002-9629(15)40499-9","article-title":"Why is left ventricular hypertrophy so predictive of morbidity and mortality?","volume":"317","author":"EJ Benjamin","year":"1999","journal-title":"The American journal of the medical sciences"},{"issue":"22","key":"ref2","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1056\/NEJM199005313222203","article-title":"Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study","volume":"322","author":"D Levy","year":"1990","journal-title":"N Engl J Med"},{"issue":"16","key":"ref3","doi-asserted-by":"crossref","first-page":"e240","DOI":"10.1161\/CIR.0b013e31829e8807","article-title":"2013 ACCF\/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation\/American Heart Association Task Force on practice guidelines","volume":"128","author":"CW Yancy","year":"2013","journal-title":"Circulation"},{"issue":"4","key":"ref4","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1161\/CIRCRESAHA.107.168336","article-title":"G protein-coupled receptor kinase 2 ablation in cardiac myocytes before or after myocardial infarction prevents heart failure","volume":"103","author":"PW Raake","year":"2008","journal-title":"Circ Res"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"264","DOI":"10.3389\/fphys.2013.00264","article-title":"Targeting cardiac beta-adrenergic signaling via GRK2 inhibition for heart failure therapy","volume":"4","author":"A Cannavo","year":"2013","journal-title":"Frontiers in physiology"},{"issue":"8","key":"ref6","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1161\/01.RES.0000037000.74258.03","article-title":"Regulation of G protein-coupled receptor signaling by scaffold proteins","volume":"91","author":"RA Hall","year":"2002","journal-title":"Circ Res"},{"issue":"10","key":"ref7","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1038\/35094577","article-title":"Classical and new roles of beta-arrestins in the regulation of G-protein-coupled receptors","volume":"2","author":"KL Pierce","year":"2001","journal-title":"Nature reviews Neuroscience"},{"issue":"18","key":"ref8","doi-asserted-by":"crossref","first-page":"1953","DOI":"10.1161\/CIRCULATIONAHA.110.988642","article-title":"G protein-coupled receptor kinase 2 activity impairs cardiac glucose uptake and promotes insulin resistance after myocardial ischemia","volume":"123","author":"M Ciccarelli","year":"2011","journal-title":"Circulation"},{"issue":"17","key":"ref9","doi-asserted-by":"crossref","first-page":"2108","DOI":"10.1161\/CIRCULATIONAHA.111.044255","article-title":"Cardiac G-protein-coupled receptor kinase 2 ablation induces a novel Ca2+ handling phenotype resistant to adverse alterations and remodeling after myocardial infarction","volume":"125","author":"PW Raake","year":"2012","journal-title":"Circulation"},{"issue":"8","key":"ref10","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1161\/CIRCRESAHA.112.300754","article-title":"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","volume":"112","author":"M Chen","year":"2013","journal-title":"Circ Res"},{"issue":"12","key":"ref11","doi-asserted-by":"crossref","first-page":"7000","DOI":"10.1073\/pnas.95.12.7000","article-title":"Expression of a beta-adrenergic receptor kinase 1 inhibitor prevents the development of myocardial failure in gene-targeted mice","volume":"95","author":"HA Rockman","year":"1998","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"2","key":"ref12","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1161\/01.CIR.87.2.454","article-title":"Altered expression of beta-adrenergic receptor kinase and beta 1-adrenergic receptors in the failing human heart","volume":"87","author":"M Ungerer","year":"1993","journal-title":"Circulation"},{"issue":"19","key":"ref13","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1093\/eurheartj\/ehr447","article-title":"AAV6.betaARKct cardiac gene therapy ameliorates cardiac function and normalizes the catecholaminergic axis in a clinically relevant large animal heart failure model","volume":"34","author":"PW Raake","year":"2013","journal-title":"Eur Heart J"},{"issue":"5215","key":"ref14","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1126\/science.7761854","article-title":"Cardiac function in mice overexpressing the beta-adrenergic receptor kinase or a beta ARK inhibitor","volume":"268","author":"WJ Koch","year":"1995","journal-title":"Science"},{"issue":"9","key":"ref15","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1161\/01.RES.0000247932.71270.2c","article-title":"Cardiac-specific ablation of G-protein receptor kinase 2 redefines its roles in heart development and beta-adrenergic signaling","volume":"99","author":"SJ Matkovich","year":"2006","journal-title":"Circ Res"},{"issue":"5363","key":"ref16","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1126\/science.280.5363.574","article-title":"Targeting the receptor-Gq interface to inhibit in vivo pressure overload myocardial hypertrophy","volume":"280","author":"SA Akhter","year":"1998","journal-title":"Science"},{"issue":"1","key":"ref17","doi-asserted-by":"crossref","first-page":"H429","DOI":"10.1152\/ajpheart.2000.279.1.H429","article-title":"Culture and adenoviral infection of adult mouse cardiac myocytes: methods for cellular genetic physiology","volume":"279","author":"YY Zhou","year":"2000","journal-title":"American journal of physiology Heart and circulatory physiology"},{"issue":"48","key":"ref18","doi-asserted-by":"crossref","first-page":"48404","DOI":"10.1074\/jbc.M308587200","article-title":"Extracellular S100A1 protein inhibits apoptosis in ventricular cardiomyocytes via activation of the extracellular signal-regulated protein kinase 1\/2 (ERK1\/2)","volume":"278","author":"P Most","year":"2003","journal-title":"J Biol Chem"},{"issue":"11","key":"ref19","doi-asserted-by":"crossref","first-page":"6403","DOI":"10.1074\/jbc.271.11.6403","article-title":"Characterization of the G protein-coupled receptor kinase GRK4. Identification of four splice variants","volume":"271","author":"RT Premont","year":"1996","journal-title":"J Biol Chem"},{"issue":"2","key":"ref20","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/S0092-8674(00)81573-1","article-title":"A calcineurin-dependent transcriptional pathway for cardiac hypertrophy","volume":"93","author":"JD Molkentin","year":"1998","journal-title":"Cell"},{"issue":"18","key":"ref21","doi-asserted-by":"crossref","first-page":"1818","DOI":"10.2174\/138161211796390976","article-title":"Phosphoinositide-3 kinase signaling in cardiac hypertrophy and heart failure","volume":"17","author":"T Aoyagi","year":"2011","journal-title":"Current pharmaceutical design"},{"issue":"3","key":"ref22","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1152\/physrev.00024.2010","article-title":"Myocardial AKT: the omnipresent nexus","volume":"91","author":"MA Sussman","year":"2011","journal-title":"Physiol Rev"},{"issue":"22","key":"ref23","doi-asserted-by":"crossref","first-page":"18953","DOI":"10.1074\/jbc.M102376200","article-title":"Agonist-dependent recruitment of phosphoinositide 3-kinase to the membrane by beta-adrenergic receptor kinase 1. A role in receptor sequestration","volume":"276","author":"SV Naga Prasad","year":"2001","journal-title":"J Biol Chem"},{"issue":"1","key":"ref24","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1161\/01.RES.0000109415.17511.18","article-title":"Calcineurin\/NFAT coupling participates in pathological, but not physiological, cardiac hypertrophy","volume":"94","author":"BJ Wilkins","year":"2004","journal-title":"Circ Res"},{"issue":"27","key":"ref25","doi-asserted-by":"crossref","first-page":"17223","DOI":"10.1074\/jbc.272.27.17223","article-title":"Mechanism of beta-adrenergic receptor desensitization in cardiac hypertrophy is increased beta-adrenergic receptor kinase","volume":"272","author":"DJ Choi","year":"1997","journal-title":"J Biol Chem"},{"issue":"8","key":"ref26","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1007\/s12265-015-9646-0","article-title":"Integrating GRK2 and NFkappaB in the Pathophysiology of Cardiac Hypertrophy","volume":"8","author":"D Sorriento","year":"2015","journal-title":"Journal of cardiovascular translational research"},{"issue":"5754","key":"ref27","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.1126\/science.1118890","article-title":"Snapshot of activated G proteins at the membrane: the Galphaq-GRK2-Gbetagamma complex","volume":"310","author":"VM Tesmer","year":"2005","journal-title":"Science"},{"issue":"17","key":"ref28","doi-asserted-by":"crossref","first-page":"2083","DOI":"10.1161\/01.CIR.101.17.2083","article-title":"Analysis of the Human G Protein-Coupled Receptor Kinase 2 (GRK2) Gene Promoter: Regulation by Signal Transduction Systems in Aortic Smooth Muscle Cells","volume":"101","author":"R Ramos-Ruiz","year":"2000","journal-title":"Circulation"},{"issue":"4","key":"ref29","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1111\/j.1476-5381.2010.00727.x","article-title":"The complex G protein-coupled receptor kinase 2 (GRK2) interactome unveils new physiopathological targets","volume":"160","author":"P Penela","year":"2010","journal-title":"British Journal of Pharmacology"},{"issue":"20","key":"ref30","doi-asserted-by":"crossref","first-page":"4752","DOI":"10.1038\/sj.emboj.7601351","article-title":"Mdm2 is involved in the ubiquitination and degradation of G-protein-coupled receptor kinase 2","volume":"25","author":"A Salcedo","year":"2006","journal-title":"EMBO J"},{"issue":"4","key":"ref31","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1016\/j.bbrc.2004.07.121","article-title":"Calcium-calcineurin signaling in the regulation of cardiac hypertrophy","volume":"322","author":"BJ Wilkins","year":"2004","journal-title":"Biochem Biophys Res Commun"},{"issue":"1","key":"ref32","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1146\/annurev.physiol.65.092101.142243","article-title":"CARDIAC HYPERTROPHY: The Good, the Bad, and the Ugly","volume":"65","author":"N Frey","year":"2003","journal-title":"Annual Review of Physiology"},{"issue":"24","key":"ref33","doi-asserted-by":"crossref","first-page":"3347","DOI":"10.1101\/gad.1492806","article-title":"Regulation of cardiac growth and coronary angiogenesis by the Akt\/PKB signaling pathway","volume":"20","author":"I Shiojima","year":"2006","journal-title":"Genes Dev"},{"issue":"23","key":"ref34","doi-asserted-by":"crossref","first-page":"2549","DOI":"10.1016\/j.jacc.2014.02.587","article-title":"Simultaneous adrenal and cardiac g-protein-coupled receptor-gbetagamma inhibition halts heart failure progression","volume":"63","author":"FA Kamal","year":"2014","journal-title":"J Am Coll Cardiol"},{"issue":"7","key":"ref35","doi-asserted-by":"crossref","first-page":"4693","DOI":"10.1074\/jbc.275.7.4693","article-title":"Gbetagamma-dependent phosphoinositide 3-kinase activation in hearts with in vivo pressure overload hypertrophy","volume":"275","author":"SV Naga Prasad","year":"2000","journal-title":"J Biol Chem"},{"issue":"9","key":"ref36","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1161\/CIRCRESAHA.110.221010","article-title":"Level of G protein-coupled receptor kinase-2 determines myocardial ischemia\/reperfusion injury via pro- and anti-apoptotic mechanisms","volume":"107","author":"H Brinks","year":"2010","journal-title":"Circ Res"},{"issue":"1","key":"ref37","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1161\/CIRCRESAHA.110.225201","article-title":"The inotropic peptide betaARKct improves betaAR responsiveness in normal and failing cardiomyocytes through G(betagamma)-mediated L-type calcium current disinhibition","volume":"108","author":"M Volkers","year":"2011","journal-title":"Circ Res"},{"issue":"4","key":"ref38","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1016\/j.yjmcc.2010.11.005","article-title":"\u03b2-arrestin: a signaling molecule and potential therapeutic target for heart failure","volume":"51","author":"N Noor","year":"2011","journal-title":"Journal of molecular and cellular cardiology"},{"issue":"1","key":"ref39","doi-asserted-by":"crossref","first-page":"C82","DOI":"10.1152\/ajpcell.00287.2006","article-title":"Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system","volume":"292","author":"PK Mehta","year":"2007","journal-title":"American journal of physiology Cell physiology"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0182110","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,9]],"date-time":"2020-05-09T04:41:04Z","timestamp":1588999264000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0182110"}},"subtitle":[],"editor":[{"given":"Sathyamangla Venkata","family":"Naga Prasad","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2017,7,31]]},"references-count":39,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2017,7,31]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0182110","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,7,31]]}}}