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Ouabain-regulated p...
Ouabain-regulated phosphoproteome reveals molecular mechanisms for Na+, K+-ATPase control of cell adhesion, proliferation, and survival
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- Panizza, Elena (författare)
- Karolinska Inst, Sci Life Lab, Dept Oncol Pathol, Solna, Sweden.;Cornell Univ, Ithaca, NY USA.
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- Zhang, Liang (författare)
- Karolinska Institutet
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- Fontana, Jacopo M. (författare)
- KTH,Science for Life Laboratory, SciLifeLab,Tillämpad fysik
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- Hamada, Kozo (författare)
- RIKEN, Brain Sci Inst, Lab Dev Neurobiol, Saitama, Japan.
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- Svensson, Daniel (författare)
- Karolinska Inst, Dept Womens & Childrens Hlth, Solna, Sweden.
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- Akkuratov, Evgeny E. (författare)
- KTH,Biofysik,Science for Life Laboratory, SciLifeLab
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- Scott, Lena (författare)
- Karolinska Inst, Dept Womens & Childrens Hlth, Solna, Sweden.
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- Mikoshiba, Katsuhiko (författare)
- RIKEN, Brain Sci Inst, Lab Dev Neurobiol, Saitama, Japan.
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- Brismar, Hjalmar (författare)
- Karolinska Institutet,KTH,Science for Life Laboratory, SciLifeLab,Tillämpad fysik,Karolinska Inst, Dept Womens & Childrens Hlth, Solna, Sweden.
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- Lehtio, Janne (författare)
- Karolinska Institutet
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- Aperia, Anita (författare)
- Karolinska Institutet
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Karolinska Institutet Karolinska Inst, Sci Life Lab, Dept Oncol Pathol, Solna, Sweden;Cornell Univ, Ithaca, NY USA. (creator_code:org_t)
- FEDERATION AMER SOC EXP BIOL, 2019
- 2019
- Engelska.
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Ingår i: The FASEB Journal. - : FEDERATION AMER SOC EXP BIOL. - 0892-6638 .- 1530-6860. ; 33:9, s. 10193-10206
- Relaterad länk:
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https://doi.org/10.1...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- 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-gamma (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., Lehtio, J., Aperia, A. Ouabain-regulated phosphoproteome reveals molecular mechanisms for Na+, K+-ATPase control of cell adhesion, proliferation, and survival.
Ämnesord
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Nyckelord
- calcium and calmodulin-dependent protein kinase
- phosphoproteomics
- apoptosis
- inositol triphosphate receptor
- kidney
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Panizza, Elena
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Zhang, Liang
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Fontana, Jacopo ...
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Hamada, Kozo
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Svensson, Daniel
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Akkuratov, Evgen ...
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visa fler...
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Scott, Lena
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Mikoshiba, Katsu ...
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Brismar, Hjalmar
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Lehtio, Janne
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Aperia, Anita
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visa färre...
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- NATURVETENSKAP
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Kungliga Tekniska Högskolan
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Karolinska Institutet