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To identify a novel binding partner of RCAN1, we performed yeast two\u2010hybrid screening and identified mitogen\u2010activated protein (MAP) kinase\/extracellular signal\u2010regulated kinase (ERK) kinase 1 (MEK1) as a partner. MEK1 was able to bind and phosphorylate RCAN1 in vitro and in vivo. MEK1\u2010dependent RCAN1 phosphorylation caused an increase in RCAN1 expression by increasing the protein half\u2010life. Nerve growth factor (NGF)\u2010dependent activation of the MEK1 pathway consistently induced RCAN1 expression. Moreover, we found that RCAN1 overexpression inhibited NGF\u2010induced neurite outgrowth and expression of neuronal marker genes, such as growth cone\u2010associated protein 43 (GAP43) and synapsin I, via inhibition of MEK1\u2010ERK1\/2 pathways. Our findings provide evidence that MEK1\u2010dependent RCAN1 phosphorylation acts as an important molecular mechanism in the control of neuronal differentiation.<\/jats:p>","DOI":"10.1002\/jcp.30609","type":"journal-article","created":{"date-parts":[[2021,10,19]],"date-time":"2021-10-19T01:01:10Z","timestamp":1634605270000},"page":"1406-1417","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["MAP kinase\/ERK kinase 1 (MEK1) phosphorylates regulator of calcineurin 1 (RCAN1) to regulate neuronal differentiation"],"prefix":"10.1002","volume":"237","author":[{"given":"Seon Sook","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Molecular Bioscience Kangwon National University Chuncheon Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eun Hye","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Molecular Bioscience Kangwon National University 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