De-phosphorylation of GR at Ser203 in nuclei associates with GR nuclear translocation and GLUT5 gene expression in Caco-2 cells
Abstract
Glucocorticoid hormones and p44/42 mitogen-activated protein kinase (MAPK) inactivation are considered to be important in small-intestinal differentiation/maturation. In this study, we found that co-treatment with glucocorticoid hormone agonist dexamethasone and p44/42 MAPK inhibitor PD98059 in intestinal cell line Caco-2 strongly induced GLUT5 gene expression. Glucocorticoid hormone receptor (GR) was translocated from the cytoplasm to the nucleus and de-phosphorylated at serine residue 203 in the nucleus, by combined treatment with dexamethasone and PD98059. The binding of GR, as well as acetylated histones H3 and H4, to the promoter/enhancer region of GLUT5 gene was enhanced by combined treatment with dexamethasone and PD98059. These results suggest that the inactivation of p44/42 MAP kinase enhances glucocorticoid hormone-induced GLUT5 gene expression, probably through controlling the phosphorylation at serine 203 and nuclear transport of GR, as well as histone acetylation on the promoter/enhancer region of GLUT5 gene.
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Multiple kinases differentially phosphorylate the GR at serine residues S203, S211 and S226, regulating GR nuclear translocation and GR-dependent gene transcription.
“Multiple kinases have been reported to differentially phosphorylate the GR at its serine residues, S203, S211 and S226, an effect which regulates GR nuclear translocation and GR-dependent gene transcription.25, 26, 27, 28, 29”
From Antidepressants increase human hippocampal neurogenesis by activating the glucocorticoid receptor (2011) · cites this paper as [27]
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Antidepressants increase human hippocampal neurogenesis by activating the glucocorticoid receptor
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- Authors
- Takabe, S., Mochizuki, K., & Goda, T.
- Affiliations
- Shizuoka University (JP)
- Corresponding author
- Goda, Toshinao
- Venue
- Archives of Biochemistry and Biophysics
- Publisher
- Elsevier BV
- Published
- 2008-07
- Volume
- 475
- Issue
- 1
- Pages
- 1-6
- ISSN
- 0003-9861 (ISSN-L)
- OpenAlex
- W1995094021
- Cited by
- 37
- References
- 21
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2022: 1 · 2021: 1 · 2020: 1 · 2019: 4 · 2018: 3 · 2017: 1 · 2016: 3 · 2015: 2 · 2014: 1 · 2013: 3 · 2012: 2
- FWCI
- 2.28
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of Biochemistry and Biophysics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Uehara Memorial Foundation
- Ministry of Education, Culture, Sports, Science and Technology (18590220, 18790171)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Digestive system and related health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- glucocorticoid receptor, nuclear translocation, dexamethasone, PD98059, histone acetylation, Caco-2 cells
- MeSH terms
- Cell Nucleus, Dexamethasone, Dose-Response Relationship, Drug, Flavonoids, Gene Expression Regulation, Humans, Phosphorylation, Receptors, Glucocorticoid, Serine, Caco-2 Cells, Glucose Transporter Type 5
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