{"entity": "publication", "iuid": "44056901db34455fbd66f9b9f2ee86da", "timestamp": "2026-08-29T04:16:00.968Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/44056901db34455fbd66f9b9f2ee86da.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/44056901db34455fbd66f9b9f2ee86da"}}, "title": "Ouabain-regulated phosphoproteome reveals molecular mechanisms for Na+, K+-ATPase control of cell adhesion, proliferation, and survival.", "authors": [{"family": "Panizza", "given": "Elena", "initials": "E"}, {"family": "Zhang", "given": "Liang", "initials": "L"}, {"family": "Fontana", "given": "Jacopo Maria", "initials": "JM"}, {"family": "Hamada", "given": "Kozo", "initials": "K"}, {"family": "Svensson", "given": "Daniel", "initials": "D"}, {"family": "Akkuratov", "given": "Evgeny E", "initials": "EE"}, {"family": "Scott", "given": "Lena", "initials": "L"}, {"family": "Mikoshiba", "given": "Katsuhiko", "initials": "K"}, {"family": "Brismar", "given": "Hjalmar", "initials": "H"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J"}, {"family": "Aperia", "given": "Anita", "initials": "A"}], "type": "journal article", "published": "2019-09-00", "journal": {"title": "FASEB J.", "issn": "1530-6860", "volume": "33", "issue": "9", "pages": "10193-10206", "issn-l": "0892-6638"}, "abstract": "The ion pump Na+, K+-ATPase (NKA) is a receptor for the cardiotonic steroid ouabain. Subsaturating concentration of ouabain triggers intracellular calcium oscillations, stimulates cell proliferation and adhesion, and protects from apoptosis. However, it is controversial whether ouabain-bound NKA is considered a signal transducer. To address this question, we performed a global analysis of protein phosphorylation in COS-7 cells, identifying 2580 regulated phosphorylation events on 1242 proteins upon 10- and 20-min treatment with ouabain. Regulated phosphorylated proteins include the inositol triphosphate receptor and stromal interaction molecule, which are essential for initiating calcium oscillations. Hierarchical clustering revealed that ouabain triggers a structured phosphorylation response that occurs in a well-defined, time-dependent manner and affects specific cellular processes, including cell proliferation and cell-cell junctions. We additionally identify regulation of the phosphorylation of several calcium and calmodulin-dependent protein kinases (CAMKs), including 2 sites of CAMK type II-\u03b3 (CAMK2G), a protein known to regulate apoptosis. To verify the significance of this result, CAMK2G was knocked down in primary kidney cells. CAMK2G knockdown impaired ouabain-dependent protection from apoptosis upon treatment with high glucose or serum deprivation. In conclusion, we establish NKA as the coordinator of a broad, tightly regulated phosphorylation response in cells and define CAMK2G as a downstream effector of NKA.-Panizza, E., Zhang, L., Fontana, J. M., Hamada, K., Svensson, D., Akkuratov, E. E., Scott, L., Mikoshiba, K., Brismar, H., Lehti\u00f6, J., Aperia, A. Ouabain-regulated phosphoproteome reveals molecular mechanisms for Na+, K+-ATPase control of cell adhesion, proliferation, and survival.", "doi": "10.1096/fj.201900445R", "pmid": "31199885", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC6704450"}], "notes": [], "created": "2026-08-21T12:13:05.633Z", "modified": "2026-08-21T12:13:05.648Z"}