| RRC ID |
41453
|
| 著者 |
Yoshikawa N, Makino Y, Okamoto K, Morimoto C, Makino I, Tanaka H.
|
| タイトル |
Distinct interaction of cortivazol with the ligand binding domain confers glucocorticoid receptor specificity: cortivazol is a specific ligand for the glucocorticoid receptor.
|
| ジャーナル |
J Biol Chem
|
| Abstract |
Ligand-receptor coupling is one of the important constituents of signal transduction and is essential for physiological transmission of actions of endogenous substances including steroid hormones. However, molecular mechanisms of the redundancy between glucocorticoid and mineralocorticoid actions remain unknown because of complicated cross-talk among, for example, these adrenal steroids, their cognate receptors, and target genes. Receptor-specific ligand that can distinctly modulate target gene expression should be developed to overcome this issue. In this report, we showed that a pyrazolosteroid cortivazol (CVZ) does not induce either nuclear translocation or transactivation function of the mineralocorticoid receptor (MR) but does both for the glucocorticoid receptor (GR). Moreover, deletion analysis of the C-terminal end of the GR has revealed that CVZ interacts with the distinct portion of the ligand binding domain (LBD) and differentially modulates the ligand-dependent interaction between transcription intermediary factor 2 and the LBD when compared with cortisol, dexamethasone, and aldosterone. Thus, it is indicated that CVZ may not be only a molecular probe for the analysis of the redundancy between the GR and MR in vivo but also a useful reagent to clarify structure-function relationship of the GR LBD.
|
| 巻・号 |
277(7)
|
| ページ |
5529-40
|
| 公開日 |
2002-2-15
|
| DOI |
10.1074/jbc.M107946200
|
| PII |
S0021-9258(19)82593-0
|
| PMID |
11741935
|
| MeSH |
Active Transport, Cell Nucleus
Amino Acid Sequence
Animals
Blotting, Western
CHO Cells
COS Cells
Cell Line
Cricetinae
DNA, Complementary / metabolism
Dose-Response Relationship, Drug
Gene Deletion
Genes, Reporter
Glucocorticoids / chemistry*
Glucocorticoids / metabolism*
Green Fluorescent Proteins
HSP90 Heat-Shock Proteins / metabolism
HeLa Cells
Humans
Kinetics
Ligands
Luminescent Proteins / metabolism
Microscopy, Fluorescence
Molecular Sequence Data
Mutagenesis, Site-Directed
Mutation
Plasmids / metabolism
Precipitin Tests
Pregnatrienes / chemistry*
Pregnatrienes / metabolism*
Protein Binding
Protein Structure, Tertiary
Protein Transport
Receptors, Glucocorticoid / chemistry*
Receptors, Glucocorticoid / metabolism
Recombinant Fusion Proteins / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Sequence Homology, Amino Acid
Structure-Activity Relationship
Time Factors
Transcriptional Activation
Transfection
|
| IF |
4.238
|
| 引用数 |
18
|
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
COS-7(RCB0539)
CV-1(RCB0160)
CHO
F9(RCB1555) |
