Interaction of the ligand-activated glucocorticoid receptor with the 14-3-3 eta protein.

The glucocorticoid receptor (GR) is a ligand-activated transcription factor. In this study, we used the yeast two-hybrid system to isolate cDNAs encoding proteins that interact with the human GR ligand-binding domain (LBD) in a ligand-dependent manner. One isolated cDNA from a HeLa cell library encoded the COOH-terminal portion of the ...
eta-isoform of the 14-3-3 protein (residues 187-246). Glucocorticoid agonists, triamcinolone acetonide and dexamethasone, induced the GR LBD/14-3-3eta protein fragment interaction, but an antagonist, RU486, did not. Glutathione S-transferase pull-down experiments in vitro showed that full-length 14-3-3eta protein also interacted with the activated GR. Transient transfection studies using COS-7 cells revealed a stimulatory effect of 14-3-3eta protein on transcriptional activation by the GR. The 14-3-3 family members have recently been found to associate with a number of important signaling proteins, such as protein kinase C and Raf-1, as functional modulators. Our findings suggest a novel regulatory role of 14-3-3eta protein in GR-mediated signaling pathways and also point to a mechanism whereby GR may cross-talk with other signal transduction systems.
Mesh Terms:
14-3-3 Proteins, Calcium, Calcium-Calmodulin-Dependent Protein Kinases, DNA, Complementary, Enzyme Inhibitors, Hela Cells, Humans, Phospholipases A, Phosphopyruvate Hydratase, Protein Conformation, Protein Kinase C, Proteins, Receptors, Glucocorticoid, Signal Transduction, Tyrosine 3-Monooxygenase
J. Biol. Chem.
Date: Mar. 28, 1997
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