{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T02:14:39Z","timestamp":1780107279658,"version":"3.54.0"},"reference-count":53,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2021,12,18]],"date-time":"2021-12-18T00:00:00Z","timestamp":1639785600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["297094"],"award-info":[{"award-number":["297094"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["333284"],"award-info":[{"award-number":["333284"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["268505"],"award-info":[{"award-number":["268505"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Prior studies show that glycogen synthase kinase 3\u03b2 (GSK3\u03b2) contributes to cardiac ischemic injury and cardiac hypertrophy. GSK3\u03b2 is constitutionally active and phosphorylation of GSK3\u03b2 at serine 9 (S9) inactivates the kinase and promotes cellular growth. GSK3\u03b2 is also phosphorylated at serine 389 (S389), but the significance of this phosphorylation in the heart is not known. We analyzed GSK3\u03b2 S389 phosphorylation in diseased hearts and utilized overexpression of GSK3\u03b2 carrying ser\u2192ala mutations at S9 (S9A) and S389 (S389A) to study the biological function of constitutively active GSK3\u03b2 in primary cardiomyocytes. We found that phosphorylation of GSK3\u03b2 at S389 was increased in left ventricular samples from patients with dilated cardiomyopathy and ischemic cardiomyopathy, and in hearts of mice subjected to thoracic aortic constriction. Overexpression of either GSK3\u03b2 S9A or S389A reduced the viability of cardiomyocytes subjected to hypoxia\u2013reoxygenation. Overexpression of double GSK3\u03b2 mutant (S9A\/S389A) further reduced cardiomyocyte viability. Determination of protein synthesis showed that overexpression of GSK3\u03b2 S389A or GSK3\u03b2 S9A\/S389A increased both basal and agonist-induced cardiomyocyte growth. Mechanistically, GSK3\u03b2 S389A mutation was associated with activation of mTOR complex 1 signaling. In conclusion, our data suggest that phosphorylation of GSK3\u03b2 at S389 enhances cardiomyocyte survival and protects from cardiomyocyte hypertrophy.<\/jats:p>","DOI":"10.3390\/ijms222413586","type":"journal-article","created":{"date-parts":[[2021,12,19]],"date-time":"2021-12-19T20:37:27Z","timestamp":1639946247000},"page":"13586","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["GSK3\u03b2 Serine 389 Phosphorylation Modulates Cardiomyocyte Hypertrophy and Ischemic Injury"],"prefix":"10.3390","volume":"22","author":[{"given":"Laura","family":"Vainio","sequence":"first","affiliation":[{"name":"Research Unit of Biomedicine, Department of Pharmacology and Toxicology, University of Oulu, Oulu 90220, Finland"},{"name":"Biocenter Oulu, University of Oulu, Oulu 90220, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saija","family":"Taponen","sequence":"additional","affiliation":[{"name":"Research Unit of Biomedicine, Department of Pharmacology and Toxicology, University of Oulu, Oulu 90220, Finland"},{"name":"Biocenter Oulu, University of Oulu, Oulu 90220, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1592-8306","authenticated-orcid":false,"given":"Sini M.","family":"Kinnunen","sequence":"additional","affiliation":[{"name":"Research Unit of Biomedicine, Department of Pharmacology and Toxicology, University of Oulu, Oulu 90220, Finland"},{"name":"Drug Research Program, Division of Pharmacology and Pharmacotherapy, Faculty of Pharmacy, University of Helsinki, Helsinki 00014, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eveliina","family":"Halmetoja","sequence":"additional","affiliation":[{"name":"Research Unit of Biomedicine, Department of Pharmacology and Toxicology, University of Oulu, Oulu 90220, Finland"},{"name":"Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu 90220, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoltan","family":"Szabo","sequence":"additional","affiliation":[{"name":"Research Unit of Biomedicine, Department of Pharmacology and Toxicology, University of Oulu, Oulu 90220, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarja","family":"Alakoski","sequence":"additional","affiliation":[{"name":"Research Unit of Biomedicine, Department of Pharmacology and Toxicology, University of Oulu, Oulu 90220, Finland"},{"name":"Biocenter Oulu, University of Oulu, Oulu 90220, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Ulvila","sequence":"additional","affiliation":[{"name":"Research Unit of Biomedicine, Department of Pharmacology and Toxicology, University of Oulu, Oulu 90220, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juhani","family":"Junttila","sequence":"additional","affiliation":[{"name":"Biocenter Oulu, University of Oulu, Oulu 90220, Finland"},{"name":"Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu 90220, Finland"},{"name":"Research Unit of Internal Medicine, Division of Cardiology, Oulu University Hospital and University of Oulu, Oulu 90220, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9935-6573","authenticated-orcid":false,"given":"P\u00e4ivi","family":"Lakkisto","sequence":"additional","affiliation":[{"name":"Unit of Cardiovascular Research, Minerva Institute for Medical Research, Helsinki 00014, Finland"},{"name":"Department of Clinical Chemistry and Hematology, University of Helsinki and Helsinki University Hospital, Helsinki 00014, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Magga","sequence":"additional","affiliation":[{"name":"Research Unit of Biomedicine, Department of Pharmacology and Toxicology, University of Oulu, Oulu 90220, Finland"},{"name":"Biocenter Oulu, University of Oulu, Oulu 90220, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Risto","family":"Kerkel\u00e4","sequence":"additional","affiliation":[{"name":"Research Unit of Biomedicine, Department of Pharmacology and Toxicology, University of Oulu, Oulu 90220, Finland"},{"name":"Biocenter Oulu, University of Oulu, Oulu 90220, Finland"},{"name":"Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu 90220, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,18]]},"reference":[{"key":"ref_1","first-page":"e38","article-title":"Heart Disease and Stroke Statistics-2016 Update: A Report from the American Heart Association","volume":"133","author":"Mozaffarian","year":"2016","journal-title":"Circulation"},{"key":"ref_2","unstructured":"GBD 2019 Diseases and Injuries Collaborators (2020). 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