{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T07:34:04Z","timestamp":1792136044188,"version":"4.4.0"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">ALPK3 (\u03b1 protein kinase 3) is an atypical kinase highly expressed in human and murine hearts. Biallelic loss\u2010of\u2010function mutations in ALPK3 lead to pediatric cardiomyopathy. The specific stages at which ALPK3 is essential for cardiac function and the mechanisms by which it regulates cardiac function require further exploration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      We generated ALPK3 global knockout and inducible cardiac\u2010specific knockout mice. We performed time\u2010course physiological and morphological assessments to determine ALPK3's role in neonatal and adult hearts. We also generated an\n                      <jats:italic toggle=\"no\">Alpk3<\/jats:italic>\n                      \u20103xFLAG\u2010HA knock\u2010in mouse model to determine endogenous ALPK3 localization. To investigate mechanisms of ALPK3 regulation, we performed biochemical assays and RNA sequencing experiments in global knockout mice. ALPK3 is critical for both neonatal and adult cardiac function. Loss of ALPK3 at germline and adult stages leads to dilated cardiomyopathy. Approximately 75% of germline ALPK3 mice die within 1\u2009month, while surviving mutant mice develop dilated cardiomyopathy that transitions to left ventricular hypertrophy, mirroring clinical manifestations in human patients with biallelic ALPK3 mutations. We found that ALPK3 localizes to the M\u2010band in both neonatal and adult cardiomyocytes and interacts with muscle RING\u2010finger proteins, which may regulate thick filament protein turnover.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">Our study highlights the necessity of ALPK3 in neonatal and adult cardiac function. Our data support a model in which ALPK3 serves as a scaffold protein to recruit machineries essential for regulating thick filament protein turnover.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.124.039464","type":"journal-article","created":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T06:59:38Z","timestamp":1742972378000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":7,"title":["\u03b1 Protein Kinase 3 Is Essential for Neonatal and Adult Cardiac Function"],"prefix":"10.1161","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9106-4258","authenticated-orcid":false,"given":"Wei","family":"Feng","sequence":"first","affiliation":[{"name":"University of California San Diego","place":["La Jolla, 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