ArticleProceedings of the National Academy of Sciences of the United States of America2010
Phospholipase C-gamma1 is involved in signaling the activation by high NaCl of the osmoprotective transcription factor TonEBP/OREBP.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 37 citations in OpenAlex.
- NFAT5: a stress-related transcription factor with multiple functions in health and disease.Cell stress · 2025Review
- Article
- Emerging roles of PLCγ1 in endothelial biology.Science signaling · 2021Review
- NFAT5-Mediated Signalling Pathways in Viral Infection and Cardiovascular Dysfunction.International journal of molecular sciences · 2021Review
- Photoperiod-dependent developmental reprogramming of the transcriptional response to seawater entry in Atlantic salmon (Salmo salar).G3 (Bethesda, Md.) · 2021Article
- The evolving role of TonEBP as an immunometabolic stress protein.Nature reviews. Nephrology · 2020Review
- Regulation of Inflammatory Functions of Macrophages and T Lymphocytes by NFAT5.Frontiers in immunology · 2019Review
- NFAT5 Isoform C Controls Biomechanical Stress Responses of Vascular Smooth Muscle Cells.Frontiers in physiology · 2018Article
- Osmotic regulation ofMolecular vision · 2017Article
- Peptide affinity analysis of proteins that bind to an unstructured region containing the transactivating domain of the osmoprotective transcription factor NFAT5.Physiological genomics · 2016Article
- Peptide affinity analysis of proteins that bind to an unstructured NH2-terminal region of the osmoprotective transcription factor NFAT5.Physiological genomics · 2016Article
- How do kinases contribute to tonicity-dependent regulation of the transcription factor NFAT5?World journal of nephrology · 2016Review
- Tonicity response element binding protein associated with neuronal cell death in the experimental diabetic retinopathy.International journal of ophthalmology · 2014Article
- High NaCl-induced inhibition of PTG contributes to activation of NFAT5 through attenuation of the negative effect of SHP-1.American journal of physiology. Renal physiology · 2013Article
- NFAT5 in cellular adaptation to hypertonic stress - regulations and functional significance.Journal of molecular signaling · 2013Article
- Inhibitory phosphorylation of GSK-3β by AKT, PKA, and PI3K contributes to high NaCl-induced activation of the transcription factor NFAT5 (TonEBP/OREBP).American journal of physiology. Renal physiology · 2013Article
- Mutations that reduce its specific DNA binding inhibit high NaCl-induced nuclear localization of the osmoprotective transcription factor NFAT5.American journal of physiology. Cell physiology · 2012Article
- Dual role of the ddx5/ddx17 RNA helicases in the control of the pro-migratory NFAT5 transcription factor.Oncogene · 2012Article
- Elevated extracellular glucose and uncontrolled type 1 diabetes enhance NFAT5 signaling and disrupt the transverse tubular network in mouse skeletal muscle.Experimental biology and medicine (Maywood, N.J.) · 2012Article
- NFAT5 contributes to osmolality-induced MCP-1 expression in mesothelial cells.Mediators of inflammation · 2012Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
High NaCl elevates activity of the osmoprotective transcription factor TonEBP/OREBP by increasing its phosphorylation, transactivating activity, and localization to the nucleus. We investigated the possible role in this activation of phospholipase C-gamma1 (PLC-gamma1), which has a predicted binding site at TonEBP/OREBP-phospho-Y143. We find the following. (i) Activation of TonEBP/OREBP transcriptional activity by high NaCl is reduced in PLC-gamma1 null cells and in HEK293 cells in which PLC-gamma1 is knocked down by a specific siRNA. (ii) High NaCl increases phosphorylation of TonEBP/OREBP at Y143. (iii) Wild-type PLC-gamma1 coimmunoprecipitates with wild-type TonEBP/OREBP but not TonEBP/OREBP-Y143A, and the coimmunoprecipitation is increased by high NaCl. (iv) PLC-gamma1 is part of the protein complex that associates with TonEBP/OREBP at its DNA binding site. (v) Knockdown of PLC-gamma1 or overexpression of a PLC-gamma1-SH3 deletion mutant reduces high NaCl-dependent TonEBP/OREBP transactivating activity. (vi) Nuclear localization of PLC-gamma1 is increased by high NaCl. (vii) High NaCl-induced nuclear localization of TonEBP/OREBP is reduced if cells lack PLC-gamma1, if PLC-gamma1 mutated in its SH2C domain is overexpressed, or if Y143 in TonEBP/OREBP is mutated to alanine. (viii) Expression of recombinant PLC-gamma1 restores nuclear localization of wild-type TonEBP/OREBP in PLC-gamma1 null cells but not of TonEBP/OREBP-Y143A. (ix) The PLC-gamma1 phospholipase inhibitor U72133 inhibits nuclear localization of TonEBP/OREBP but not the increase of its transactivating activity. We conclude that, when NaCl is elevated, TonEBP/OREBP becomes phosphorylated at Y143, resulting in binding of PLC-gamma1 to that site, which contributes to TonEBP/OREBP transcriptional activity, transactivating activity, and nuclear localization.
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