{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T05:03:14Z","timestamp":1789534994053,"version":"build-2803163510"},"reference-count":33,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council of Australia","doi-asserted-by":"publisher","award":["APP2004282"],"award-info":[{"award-number":["APP2004282"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council of Australia","doi-asserted-by":"publisher","award":["APP1117366"],"award-info":[{"award-number":["APP1117366"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"award":["APP2004282"],"award-info":[{"award-number":["APP2004282"]}],"id":[{"id":"https:\/\/ror.org\/011kf5r70","id-type":"ROR","asserted-by":"publisher"}]},{"award":["APP1117366"],"award-info":[{"award-number":["APP1117366"]}],"id":[{"id":"https:\/\/ror.org\/011kf5r70","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021137","name":"Woodside Energy","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100021137","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The cardiac calcium channel Cav1.2 is essential for embryonic development, cardiac excitation\u2013contraction coupling, and the \u201cFight or Flight\u201d response. Regulation of Cav1.2 by protein kinase A (PKA) phosphorylation is critical to this process, though the underlying mechanism remains contentious. We previously identified serine 1458 (S1458) in the proximal C-terminus of the human Cav1.2 as essential for PKA-mediated regulation in vitro. To investigate its functional role in vivo, we generated three mouse models targeting S1487, the mouse equivalent of human S1458. Comprehensive phenotyping and assessment of responses to \u03b2-adrenergic receptor stimulation were conducted in vivo, ex vivo, and in vitro. We demonstrate for the first time that a seven amino acid (7aa) region containing S1487 is crucial for proper channel folding, as homozygous mutant mice exhibited embryonic lethality. We confirm that phosphorylation at S1487 is necessary for altered Cav1.2 function required for the \u201cFight or Flight\u201d response, clarifying the functional significance of this region.<\/jats:p>","DOI":"10.3390\/cells15181655","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T08:10:23Z","timestamp":1789373423000},"page":"1655","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Seven Amino Acid Long Region in the Cardiac Cav1.2, Encompassing Ser1487, Is Essential for Mice Embryonic Development and \u201cFight or Flight\u201d Responses"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-4242-9780","authenticated-orcid":false,"given":"Catherine","family":"Jenkins","sequence":"first","affiliation":[{"name":"Ben Beale Laboratory in Cardiovascular Research, School of Human Sciences, The University of Western Australia, M309, 35 Stirling Highway Perth, WA 6009, Australia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0063-257X","authenticated-orcid":false,"given":"Henrietta","family":"Cserne Szappanos","sequence":"additional","affiliation":[{"name":"Ben Beale Laboratory in Cardiovascular Research, School of Human Sciences, The University of Western Australia, M309, 35 Stirling Highway Perth, WA 6009, Australia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8796-2402","authenticated-orcid":false,"given":"Agnieszka","family":"Dyrda","sequence":"additional","affiliation":[{"name":"Ben Beale Laboratory in Cardiovascular Research, School of Human Sciences, The University of Western Australia, M309, 35 Stirling Highway Perth, WA 6009, Australia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3078-4586","authenticated-orcid":false,"given":"Teagan S.","family":"Er","sequence":"additional","affiliation":[{"name":"Ben Beale Laboratory in Cardiovascular Research, School of Human Sciences, The University of Western Australia, M309, 35 Stirling Highway Perth, WA 6009, Australia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Filip","family":"van Petegem","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Livia C.","family":"Hool","sequence":"additional","affiliation":[{"name":"Ben Beale Laboratory in Cardiovascular Research, School of Human Sciences, The University of Western Australia, M309, 35 Stirling Highway Perth, WA 6009, Australia"},{"name":"Victor Chang Cardiac Research Institute, 405 Liverpool Street, Darlinghurst, NSW 2010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"39193","DOI":"10.1074\/jbc.M006467200","article-title":"Functional Embryonic Cardiomyocytes after Disruption of the L-type \u03b11C (Cav 1.2) Calcium Channel Gene in the Mouse","volume":"275","author":"Seisenberger","year":"2000","journal-title":"J. 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