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TS pathology is caused by mutations in tuberous sclerosis complex (<jats:italic>TSC<\/jats:italic>) genes and is associated with insulin resistance, decreased glycogen synthase kinase 3\u03b2 (GSK3\u03b2) activity, activation of the mammalian target of rapamycin complex 1 (mTORC1), and subsequent increase in protein synthesis. Here, we show that extracellular signal\u2013regulated kinases (ERK1\/2) respond to insulin stimulation and integrate insulin signaling to phosphorylate and thus inactivate GSK3\u03b2, resulting in increased protein synthesis that is independent of Akt\/mTORC1 activity. Inhibition of ERK1\/2 in <jats:italic>Tsc2<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> cells\u2014a model of TS\u2014rescues GSK3\u03b2 activity and protein synthesis levels, thus highlighting ERK1\/2 as a potential therapeutic target for the treatment of TS.<\/jats:p>","DOI":"10.1038\/s41598-017-04528-5","type":"journal-article","created":{"date-parts":[[2017,6,19]],"date-time":"2017-06-19T11:46:18Z","timestamp":1497872778000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Inhibition of ERK1\/2 Restores GSK3\u03b2 Activity and Protein Synthesis Levels in a Model of Tuberous Sclerosis"],"prefix":"10.1038","volume":"7","author":[{"given":"Rituraj","family":"Pal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vitaliy V.","family":"Bondar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn J.","family":"Adamski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George G.","family":"Rodney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Sardiello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,6,23]]},"reference":[{"key":"4528_CR1","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1038\/nature10658","volume":"480","author":"BD Auerbach","year":"2011","unstructured":"Auerbach, B. 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