{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:48:02Z","timestamp":1787028482740,"version":"build-2736575974"},"reference-count":45,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2022,8,25]],"date-time":"2022-08-25T00:00:00Z","timestamp":1661385600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute for Biotechnology in the Negev (NIBN)","award":["R01HL158052"],"award-info":[{"award-number":["R01HL158052"]}]},{"name":"Gassner Fund for Medical Research","award":["R01HL158052"],"award-info":[{"award-number":["R01HL158052"]}]},{"name":"NIH","award":["R01HL158052"],"award-info":[{"award-number":["R01HL158052"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Dedicator of cytokinesis 10 (Dock10) is a guanine nucleotide exchange factor for Cdc42 and Rac1 that regulates the JNK (c-Jun N-terminal kinase) and p38 MAPK (mitogen-activated protein kinase) signaling cascades. In this study, we characterized the roles of Dock10 in the myocardium. In vitro: we ablated Dock10 in neonatal mouse floxed Dock10 cardiomyocytes (NMCMs) and cardiofibroblasts (NMCFs) by transduction with an adenovirus expressing Cre-recombinase. In vivo, we studied mice in which the Dock10 gene was constitutively and globally deleted (Dock10 KO) and mice with cardiac myocyte-specific Dock10 KO (Dock10 CKO) at baseline and in response to two weeks of Angiotensin II (Ang II) infusion. In vitro, Dock10 ablation differentially inhibited the \u03b1-adrenergic stimulation of p38 and JNK in NMCM and NMCF, respectively. In vivo, the stimulation of both signaling pathways was markedly attenuated in the heart. The Dock10 KO mice had normal body weight and cardiac size. However, echocardiography revealed mildly reduced systolic function, and IonOptix recordings demonstrated reduced contractility and elevated diastolic calcium levels in isolated cardiomyocytes. Remarkably, Dock10 KO, but not Dock10 CKO, exaggerated the pathological response to Ang II infusion. These data suggest that Dock10 regulates cardiac stress-related signaling. Although Dock10 can regulate MAPK signaling in both cardiomyocytes and cardiofibroblasts, the inhibition of pathological cardiac remodeling is not apparently due to the Dock10 signaling in the cardiomyocyte.<\/jats:p>","DOI":"10.3390\/ijms23179616","type":"journal-article","created":{"date-parts":[[2022,8,25]],"date-time":"2022-08-25T21:28:12Z","timestamp":1661462892000},"page":"9616","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Dock10 Regulates Cardiac Function under Neurohormonal Stress"],"prefix":"10.3390","volume":"23","author":[{"given":"Liad","family":"Segal","sequence":"first","affiliation":[{"name":"Department of Physiology and Cell Biology, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel"},{"name":"Regenerative Medicine and Stem Cell (RMSC) Research Center, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Etzion","sequence":"additional","affiliation":[{"name":"Regenerative Medicine and Stem Cell (RMSC) Research Center, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigal","family":"Elyagon","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cell Biology, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel"},{"name":"Regenerative Medicine and Stem Cell (RMSC) Research Center, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moran","family":"Shahar","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cell Biology, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8783-9364","authenticated-orcid":false,"given":"Hadar","family":"Klapper-Goldstein","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cell Biology, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel"},{"name":"Regenerative Medicine and Stem Cell (RMSC) Research Center, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aviva","family":"Levitas","sequence":"additional","affiliation":[{"name":"Pediatric Cardiology Department, Soroka University Medical Center, Beer-Sheva 8410501, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S.","family":"Kapiloff","sequence":"additional","affiliation":[{"name":"Departments of Ophthalmology and Medicine (Cardiovascular Medicine), Stanford Cardiovascular Institute, Stanford University, Palo Alto 94304-1209, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0656-3096","authenticated-orcid":false,"given":"Ruti","family":"Parvari","sequence":"additional","affiliation":[{"name":"The Shraga Segal Department of Microbiology, Immunology and Genetics, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel"},{"name":"National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9930-1035","authenticated-orcid":false,"given":"Yoram","family":"Etzion","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cell Biology, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel"},{"name":"Regenerative Medicine and Stem Cell (RMSC) Research Center, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1172\/JCI62839","article-title":"Signaling effectors underlying pathologic growth and remodeling of the heart","volume":"123","author":"Maillet","year":"2013","journal-title":"J. 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