ArticleThe Journal of biological chemistry2008
Phosphorylation by casein kinase 1 regulates tonicity-induced osmotic response element-binding protein/tonicity enhancer-binding protein nucleocytoplasmic trafficking.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 40 citations in OpenAlex.
- NFAT5: a stress-related transcription factor with multiple functions in health and disease.Cell stress · 2025Review
- Unconventional tonicity-regulated nuclear trafficking of NFAT5 mediated by KPNB1, XPOT and RUVBL2.Journal of cell science · 2022Article
- NFAT5-Mediated Signalling Pathways in Viral Infection and Cardiovascular Dysfunction.International journal of molecular sciences · 2021Review
- Potential Role of Gene Regulator NFAT5 in the Pathogenesis of Diabetes Mellitus.Journal of diabetes research · 2020Review
- Regulation of Inflammatory Functions of Macrophages and T Lymphocytes by NFAT5.Frontiers in immunology · 2019Review
- Osmolality/salinity-responsive enhancers (OSREs) control induction of osmoprotective genes in euryhaline fish.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Macromolecular crowding effect is critical for maintaining SIRT1's nuclear localization in cancer cells.Cell cycle (Georgetown, Tex.) · 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
- The CK1 Family: Contribution to Cellular Stress Response and Its Role in Carcinogenesis.Frontiers in oncology · 2014Review
- 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
- The role of hyperosmotic stress in inflammation and disease.Biomolecular concepts · 2012Article
- Single-step inline hydroxyapatite enrichment facilitates identification and quantitation of phosphopeptides from mass-limited proteomes with MudPIT.Journal of proteome research · 2012Article
- Placental TonEBP/NFAT5 osmolyte regulation in an ovine model of intrauterine growth restriction.Biology of reproduction · 2012Article
- Nuclear factor of activated T cells 5 regulates vascular smooth muscle cell phenotypic modulation.Arteriosclerosis, thrombosis, and vascular biology · 2011Article
- High NaCl-induced activation of CDK5 increases phosphorylation of the osmoprotective transcription factor TonEBP/OREBP at threonine 135, which contributes to its rapid nuclear localization.Molecular biology of the cell · 2011Article
- Widespread protein aggregation as an inherent part of aging in C. elegans.PLoS biology · 2010Article
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Authors and funding
7 authors at 4 institutions in 4 countries.
Funding
Abstract
The osmotic response element-binding protein (OREBP), also known as tonicity enhancer-binding protein (TonEBP) or NFAT5, is the only known osmo-sensitive transcription factor that mediates cellular adaptations to extracellular hypertonic stress. Although it is well documented that the subcellular localization and transactivation activity of OREBP/TonEBP are tightly regulated by extracellular tonicity, the molecular mechanisms involved remain elusive. Here we show that nucleocytoplasmic trafficking of OREBP/TonEBP is regulated by the dual phosphorylation of Ser-155 and Ser-158. Alanine scanning mutagenesis revealed that Ser-155 is an essential residue that regulates OREBP/TonEBP nucleocytoplasmic trafficking. Tandem mass spectrometry revealed that Ser-155 and Ser-158 of OREBP/TonEBP are both phosphorylated in living cells under hypotonic conditions. In vitro phosphorylation assays further suggest that phosphorylation of the two serine residues proceeds in a hierarchical manner with phosphorylation of Ser-155 priming the phosphorylation of Ser-158 and that these phosphorylations are essential for nucleocytoplasmic trafficking of the transcription factor. Finally, we have shown that the pharmacological inhibition of casein kinase 1 (CK1) abolishes the phosphorylation of Ser-158 and impedes OREBP/TonEBP nuclear export and that recombinant CK1 phosphorylates Ser-158. Knockdown of CK1alpha1L, a novel isoform of CK1, inhibits hypotonicity-induced OREBP/TonEBP nuclear export. Together these data highlight the importance of Ser-155 and Ser-158 in the nucleocytoplasmic trafficking of OREBP/TonEBP and indicate that CK1 plays a major role in regulating this process.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.