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This disorder is caused by an abnormal expansion of the CTG triplet at the DMPK gene that, when transcribed to expanded mRNA, can lead to RNA toxic gain of function, alternative splicing impairments, and dysfunction of different signaling pathways, many regulated by protein phosphorylation. In order to deeply characterize the protein phosphorylation alterations in DM1, a systematic review was conducted through PubMed and Web of Science databases. From a total of 962 articles screened, 41 were included for qualitative analysis, where we retrieved information about total and phosphorylated levels of protein kinases, protein phosphatases, and phosphoproteins in DM1 human samples and animal and cell models. Twenty-nine kinases, 3 phosphatases, and 17 phosphoproteins were reported altered in DM1. Signaling pathways that regulate cell functions such as glucose metabolism, cell cycle, myogenesis, and apoptosis were impaired, as seen by significant alterations to pathways such as AKT\/mTOR, MEK\/ERK, PKC\/CUGBP1, AMPK, and others in DM1 samples. This explains the complexity of DM1 and its different manifestations and symptoms, such as increased insulin resistance and cancer risk. Further studies can be done to complement and explore in detail specific pathways and how their regulation is altered in DM1, to find what key phosphorylation alterations are responsible for these manifestations, and ultimately to find therapeutic targets for future treatments.<\/jats:p>","DOI":"10.3390\/ijms24043091","type":"journal-article","created":{"date-parts":[[2023,2,6]],"date-time":"2023-02-06T02:57:32Z","timestamp":1675652252000},"page":"3091","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Protein Phosphorylation Alterations in Myotonic Dystrophy Type 1: A Systematic Review"],"prefix":"10.3390","volume":"24","author":[{"given":"Adriana","family":"Costa","sequence":"first","affiliation":[{"name":"Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"given":"Ana C.","family":"Cruz","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3277-1809","authenticated-orcid":false,"given":"Filipa","family":"Martins","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5862-5797","authenticated-orcid":false,"given":"Sandra","family":"Rebelo","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, 3810-193 Aveiro, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1017\/cjn.2015.311","article-title":"A Systematic Review and Meta-analysis on the Epidemiology of the Muscular Dystrophies","volume":"43","author":"Mah","year":"2015","journal-title":"Can. 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