PMID- 12021388
OWN - NLM
STAT- MEDLINE
DCOM- 20020617
LR  - 20211203
IS  - 0026-895X (Print)
IS  - 0026-895X (Linking)
VI  - 61
IP  - 6
DP  - 2002 Jun
TI  - Residue threonine 350 confers steroid hormone responsiveness to the mouse nuclear 
      orphan receptor CAR.
PG  - 1284-8
AB  - Steroid hormones modulate activity of the nuclear receptor constitutive active 
      receptor (CAR, or constitutive androstane receptor) in mouse liver. Progesterone 
      and testosterone repress the constitutive activity of mouse CAR (mCAR) in 
      cell-mediated transfection assays, whereas estrogens activate the repressed 
      receptor. This repression and activation is not observed with human CAR. To 
      define the structural basis that confers the hormone responsiveness to mCAR, we 
      constructed various chimeric and mutated receptors and examined their response to 
      steroid hormones. The hormone responsiveness resided near or within AF-2 domain 
      of mCAR. Moreover, a single mutation of threonine at position 350 to the 
      corresponding methionine in the human counterpart abolished the repression of 
      mCAR by steroid hormones. Coactivation by steroid receptor coactivator 1 (SRC-1) 
      of mCAR did not depend on the threonine 350. However, overexpression of SRC-1 
      counteracted progesterone to repress mCAR activity. Thus, threonine 350 seems to 
      regulate hormone responsiveness of mCAR by interfering indirectly an interaction 
      of the receptor with a coactivator.
FAU - Ueda, Akiko
AU  - Ueda A
AD  - Pharmacogenetics Section, Laboratory of Reproductive and Developmental 
      Toxicology, National Institute of Environmental Health Sciences, National 
      Institutes of Health, Research Triangle Park, North Carolina 27709, USA.
FAU - Kakizaki, Satoru
AU  - Kakizaki S
FAU - Negishi, Masahiko
AU  - Negishi M
FAU - Sueyoshi, Tatsuya
AU  - Sueyoshi T
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Mol Pharmacol
JT  - Molecular pharmacology
JID - 0035623
RN  - 0 (Constitutive Androstane Receptor)
RN  - 0 (Estrogens)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Steroids)
RN  - 0 (Transcription Factors)
RN  - 2ZD004190S (Threonine)
RN  - 3XMK78S47O (Testosterone)
RN  - 4G7DS2Q64Y (Progesterone)
SB  - IM
MH  - Amino Acid Substitution
MH  - Animals
MH  - Constitutive Androstane Receptor
MH  - Estrogens/pharmacology
MH  - Humans
MH  - Mice
MH  - Mutagenesis, Site-Directed
MH  - Progesterone/pharmacology
MH  - Receptors, Cytoplasmic and Nuclear/drug effects/genetics/*metabolism
MH  - Recombinant Fusion Proteins/genetics/metabolism
MH  - Steroids/*pharmacology
MH  - Testosterone/pharmacology
MH  - Threonine/genetics/*metabolism
MH  - Transcription Factors/drug effects/genetics/*metabolism
MH  - Tumor Cells, Cultured
EDAT- 2002/05/22 10:00
MHDA- 2002/06/18 10:01
CRDT- 2002/05/22 10:00
PHST- 2002/05/22 10:00 [pubmed]
PHST- 2002/06/18 10:01 [medline]
PHST- 2002/05/22 10:00 [entrez]
AID - 10.1124/mol.61.6.1284 [doi]
PST - ppublish
SO  - Mol Pharmacol. 2002 Jun;61(6):1284-8. doi: 10.1124/mol.61.6.1284.