{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T06:14:02Z","timestamp":1791526442539,"version":"4.3.4"},"reference-count":32,"publisher":"National Academy of Sciences","issue":"35","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2007,8,28]]},"abstract":"<jats:p>\n                    MAPK signaling pathways function as critical regulators of cellular differentiation, proliferation, stress responsiveness, and apoptosis. One branch of the MAPK signaling pathway that culminates in ERK1\/2 activation is hypothesized to regulate the growth and adaptation of the heart to both physiologic and pathologic stimuli, given its known activation in response to virtually every stress- and agonist-induced hypertrophic stimulus examined to date. Here we investigated the requirement of ERK1\/2 signaling in mediating the cardiac hypertrophic growth response in\n                    <jats:italic>Erk1<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    and\n                    <jats:italic>Erk2<\/jats:italic>\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    mice, as well as in transgenic mice with inducible expression of an ERK1\/2-inactivating phosphatase in the heart, dual-specificity phosphatase 6. Although inducible expression of dual-specificity phosphatase 6 in the heart eliminated ERK1\/2 phosphorylation at baseline and after stimulation without affecting any other MAPK, it did not diminish the hypertrophic response to pressure overload stimulation, neuroendocrine agonist infusion, or exercise. Similarly,\n                    <jats:italic>Erk1<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    and\n                    <jats:italic>Erk2<\/jats:italic>\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    mice showed no reduction in pathologic or physiologic stimulus-induced cardiac growth\n                    <jats:italic>in vivo<\/jats:italic>\n                    . However, blockade or deletion of cardiac ERK1\/2 did predispose the heart to decompensation and failure after long-term pressure overload in conjunction with an increase in myocyte TUNEL. Thus, ERK1\/2 signaling is not required for mediating physiologic or pathologic cardiac hypertrophy\n                    <jats:italic>in vivo<\/jats:italic>\n                    , although it does play a protective role in response to pathologic stimuli.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0610906104","type":"journal-article","created":{"date-parts":[[2007,8,20]],"date-time":"2007-08-20T21:15:00Z","timestamp":1187644500000},"page":"14074-14079","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":229,"title":["Genetic inhibition of cardiac ERK1\/2 promotes stress-induced apoptosis and heart failure but has no effect on hypertrophy\n                    <i>in vivo<\/i>"],"prefix":"10.1073","volume":"104","author":[{"given":"Nicole H.","family":"Purcell","sequence":"first","affiliation":[{"name":"*Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, 3333 Burnet Avenue, Cincinnati, OH 45229; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin J.","family":"Wilkins","sequence":"additional","affiliation":[{"name":"*Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, 3333 Burnet Avenue, Cincinnati, OH 45229; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allen","family":"York","sequence":"additional","affiliation":[{"name":"*Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, 3333 Burnet Avenue, Cincinnati, OH 45229; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc K.","family":"Saba-El-Leil","sequence":"additional","affiliation":[{"name":"Institut de Recherche en Immunologie et Canc\u00e9rologie and Departments of Pharmacology and Molecular Biology, Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, QC, Canada H3C 3J7"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvain","family":"Meloche","sequence":"additional","affiliation":[{"name":"Institut de Recherche en Immunologie et Canc\u00e9rologie and Departments of Pharmacology and Molecular Biology, Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, QC, Canada H3C 3J7"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Robbins","sequence":"additional","affiliation":[{"name":"*Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, 3333 Burnet Avenue, Cincinnati, OH 45229; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffery D.","family":"Molkentin","sequence":"additional","affiliation":[{"name":"*Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, 3333 Burnet Avenue, Cincinnati, OH 45229; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2007,8,28]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/0735-1097(93)90455-A"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199005313222203"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-198706106-00009"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.2001.90.5.1900"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1983"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0955-0674(99)80028-3"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.83.4.345"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.embor.7400755"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2003.12.008"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000038488.38975.1A"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.23.6341"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000127126.73759.23"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.10.6749"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M303909200"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M103369200"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M009753200"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0510506103"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000065442.64694.9F"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.15.8951"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.78.6.954"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.142.2.523"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.2000.1135"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.126.6.1565"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)43853-7"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000138190.50127.6A"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2005.03.024"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.115.8.1575"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.embor.embor939"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.286.5443.1374"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000109415.17511.18"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000215985.18538.c4"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.3.1196"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0610906104","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T15:15:02Z","timestamp":1649776502000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0610906104"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,8,28]]},"references-count":32,"journal-issue":{"issue":"35","published-print":{"date-parts":[[2007,8,28]]}},"alternative-id":["10.1073\/pnas.0610906104"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0610906104","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,8,28]]},"assertion":[{"value":"2006-12-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2007-08-28","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}