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Analysis of different stages in thrombopoiesis reveals that MT has the capacity to promote the expansion of CD34<jats:sup>+<\/jats:sup> and CD41<jats:sup>+<\/jats:sup> cells, and accelerate proplatelet formation (PPF) and platelet production. Furthermore, in vivo experiments show that MT has a potential therapeutic effect on radiation\u2010induced thrombocytopenia. The underlying mechanism suggests that both extracellular signal\u2010regulated kinase 1\/2 (ERK1\/2) and Akt signaling are involved in the processes of thrombopoiesis facilitated by MT. Interestingly, in addition to the direct regulation of Akt signaling by its upstream phosphoinositide 3\u2010kinase (PI3K), ERK1\/2 signaling is also regulated by PI3K via its effector, dual adaptor for phosphotyrosine and 3\u2010phosphoinositides (DAPP1), in megakaryocytes after MT treatment. Moreover, the expression level of DAPP1 during megakaryocyte differentiation is closely related to the activation of ERK1\/2 and Akt at different stages of thrombopoiesis. In conclusion, our data suggest that MT treatment can promote thrombopoiesis, which is modulated by the DAPP1\u2010orchestrated activation of ERK1\/2 and Akt signaling.<\/jats:p>","DOI":"10.1111\/jpi.12637","type":"journal-article","created":{"date-parts":[[2020,2,13]],"date-time":"2020-02-13T04:35:07Z","timestamp":1581568507000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Melatonin enhances thrombopoiesis through ERK1\/2 and Akt activation orchestrated by dual adaptor for phosphotyrosine and 3\u2010phosphoinositides"],"prefix":"10.1111","volume":"68","author":[{"given":"Shilei","family":"Chen","sequence":"first","affiliation":[{"name":"State Key Laboratory of Trauma, Burns and Combined Injury Institute of Combined Injury Chongqing Engineering Research Center for Nanomedicine College of Preventive Medicine Third Military Medical University Chongqing 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