{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T12:31:01Z","timestamp":1789475461955,"version":"build-2803163510"},"reference-count":84,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2022,9,3]],"date-time":"2022-09-03T00:00:00Z","timestamp":1662163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Russian Science Foundation","award":["#19-74-30007"],"award-info":[{"award-number":["#19-74-30007"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Beta-amyloid (A\u03b2) has a dual role, both as an important factor in the pathology of Alzheimer\u2019s disease and as a regulator in brain physiology. The inhibitory effect of A\u03b242 oligomers on Na,K-ATPase contributes to neuronal dysfunction in Alzheimer\u2019s disease. Still, the physiological role of the monomeric form of A\u03b242 interaction with Na,K-ATPase remains unclear. We report that Na,K-ATPase serves as a receptor for A\u03b242 monomer, triggering Src kinase activation. The co-localization of A\u03b242 with \u03b11- and \u03b21-subunits of Na,K-ATPase, and Na,K-ATPase with Src kinase in SH-SY5Y neuroblastoma cells, was observed. Treatment of cells with 100 nM A\u03b242 causes Src kinase activation, but does not alter Na,K-ATPase transport activity. The interaction of A\u03b242 with \u03b11\u03b21 Na,K-ATPase isozyme leads to activation of Src kinase associated with the enzyme. Notably, prevention of Na,K-ATPase:Src kinase interaction by a specific inhibitor pNaKtide disrupts the A\u03b2-induced Src kinase activation. Stimulatory effect of A\u03b242 on Src kinase was lost under hypoxic conditions, which was similar to the effect of specific Na,K-ATPase ligands, the cardiotonic steroids. Our findings identify Na,K-ATPase as a A\u03b242 receptor, thus opening a prospect on exploring the physiological and pathological Src kinase activation caused by A\u03b242 in the nervous system.<\/jats:p>","DOI":"10.3390\/cells11172753","type":"journal-article","created":{"date-parts":[[2022,9,5]],"date-time":"2022-09-05T20:48:25Z","timestamp":1662410905000},"page":"2753","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Na,K-ATPase Acts as a Beta-Amyloid Receptor Triggering Src Kinase Activation"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0787-415X","authenticated-orcid":false,"given":"Irina Yu.","family":"Petrushanko","sequence":"first","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6203-8125","authenticated-orcid":false,"given":"Artem M.","family":"Tverskoi","sequence":"additional","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evgeny P.","family":"Barykin","sequence":"additional","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9202-0727","authenticated-orcid":false,"given":"Aleksandra V.","family":"Petrovskaya","sequence":"additional","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4311-5065","authenticated-orcid":false,"given":"Maria A.","family":"Strelkova","sequence":"additional","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga G.","family":"Leonova","sequence":"additional","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1763-300X","authenticated-orcid":false,"given":"Anastasia A.","family":"Anashkina","sequence":"additional","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna P.","family":"Tolstova","sequence":"additional","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5000-1373","authenticated-orcid":false,"given":"Alexei A.","family":"Adzhubei","sequence":"additional","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia"},{"name":"Department of Microbiology, Immunology, and Tropical Medicine, Washington University School of Medicine and Health Sciences, Washington, DC 63110-1010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0502-5381","authenticated-orcid":false,"given":"Anna Yu.","family":"Bogdanova","sequence":"additional","affiliation":[{"name":"Institute of Veterinary Physiology, Vetsuisse Faculty and the Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, CH-8057 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander A.","family":"Makarov","sequence":"additional","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1517-1983","authenticated-orcid":false,"given":"Vladimir A.","family":"Mitkevich","sequence":"additional","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1126\/science.1131864","article-title":"Exogenous induction of cerebral beta-amyloidogenesis is governed by agent and host","volume":"313","author":"Coomaraswamy","year":"2006","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1126\/science.1222951","article-title":"Cell biology. 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