De-phosphorylation of GR at Ser203 in nuclei associates with GR nuclear translocation and GLUT5 gene expression in Caco-2 cells.
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.
Takabe
Satsuki
S
Laboratory of Nutritional Physiology, Graduate School of Nutritional and Environmental Sciences and Global COE, The University of Shizuoka, 52-1 Yada, Shizuoka-shi, Shizuoka 422-8526, Japan.
Mochizuki
Kazuki
K
Goda
Toshinao
T
D018938:Caco-2 Cells; D002467:Cell Nucleus; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D051296:Glucose Transporter Type 5 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation; D011965:Receptors, Glucocorticoid / Q000378:metabolism / Q000502:physiology*; D012694:Serine / Q000378:metabolism*
D005419:Flavonoids; D051296:Glucose Transporter Type 5; D011965:Receptors, Glucocorticoid; C495726:SLC2A5 protein, human; D012694:Serine; D003907:Dexamethasone; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one