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Hypertrophy underlies postnatal heart growth and is triggered after stress, but the molecular mechanisms involved in these processes are largely unknown. Here we show that cardiac activation of p38\u03b3 and p38\u03b4 increases during postnatal development and by hypertrophy-inducing stimuli. p38\u03b3\/\u03b4 promote cardiac hypertrophy by phosphorylating the mTORC1 and mTORC2 inhibitor DEPTOR, which leads to its degradation and mTOR activation. Hearts from mice lacking one or both kinases are below normal size, have high levels of DEPTOR, low activity of the mTOR pathway and reduced protein synthesis. The phenotype of\n                    <jats:italic>p38\u03b3\/\u03b4<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice is reverted by overactivation of mTOR with amino acids, shRNA-mediated knockdown of\n                    <jats:italic>Deptor<\/jats:italic>\n                    , or cardiomyocyte overexpression of active p38\u03b3 and p38\u03b4. Moreover, in WT mice, heart weight is reduced by cardiac overexpression of DEPTOR. Our results demonstrate that p38\u03b3\/\u03b4 control heart growth by modulating mTOR pathway through DEPTOR phosphorylation and subsequent degradation.\n                  <\/jats:p>","DOI":"10.1038\/ncomms10477","type":"journal-article","created":{"date-parts":[[2016,1,22]],"date-time":"2016-01-22T05:08:21Z","timestamp":1453439301000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":75,"title":["p38\u03b3 and \u03b4 promote heart hypertrophy by targeting the mTOR-inhibitory protein DEPTOR for degradation"],"prefix":"10.1038","volume":"7","author":[{"given":"B\u00e1rbara","family":"Gonz\u00e1lez-Ter\u00e1n","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan Antonio","family":"L\u00f3pez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Rodr\u00edguez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis","family":"Leiva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Mart\u00ednez-Mart\u00ednez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan Antonio","family":"Bernal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis Jes\u00fas","family":"Jim\u00e9nez-Borreguero","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan Miguel","family":"Redondo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jes\u00fas","family":"Vazquez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guadalupe","family":"Sabio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,1,22]]},"reference":[{"key":"BFncomms10477_CR1","doi-asserted-by":"publisher","first-page":"1079","DOI":"10.1161\/01.RES.0000072977.86706.23","volume":"92","author":"H Akazawa","year":"2003","unstructured":"Akazawa, H. & Komuro, I. 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