PMID- 23878391
OWN - NLM
STAT- MEDLINE
DCOM- 20131125
LR  - 20211021
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Print)
IS  - 0270-7306 (Linking)
VI  - 33
IP  - 18
DP  - 2013 Sep
TI  - Brain-derived neurotrophic factor signaling rewrites the glucocorticoid 
      transcriptome via glucocorticoid receptor phosphorylation.
PG  - 3700-14
LID - 10.1128/MCB.00150-13 [doi]
AB  - Abnormal glucocorticoid and neurotrophin signaling has been implicated in 
      numerous psychiatric disorders. However, the impact of neurotrophic signaling on 
      glucocorticoid receptor (GR)-dependent gene expression is not understood. We 
      therefore examined the impact of brain-derived neurotrophic factor (BDNF) 
      signaling on GR transcriptional regulatory function by gene expression profiling 
      in primary rat cortical neurons stimulated with the selective GR agonist 
      dexamethasone (Dex) and BDNF, alone or in combination. Simultaneous treatment 
      with BDNF and Dex elicited a unique set of GR-responsive genes associated with 
      neuronal growth and differentiation and also enhanced the induction of a large 
      number of Dex-sensitive genes. BDNF via its receptor TrkB enhanced the 
      transcriptional activity of a synthetic GR reporter, suggesting a direct effect 
      of BDNF signaling on GR function. Indeed, BDNF treatment induces the 
      phosphorylation of GR at serine 155 (S155) and serine 287 (S287). Expression of a 
      nonphosphorylatable mutant (GR S155A/S287A) impaired the induction of a subset of 
      BDNF- and Dex-regulated genes. Mechanistically, BDNF-induced GR phosphorylation 
      increased GR occupancy and cofactor recruitment at the promoter of a 
      BDNF-enhanced gene. GR phosphorylation in vivo is sensitive to changes in the 
      levels of BDNF and TrkB as well as stress. Therefore, BDNF signaling specifies 
      and amplifies the GR transcriptome through a coordinated GR 
      phosphorylation-dependent detection mechanism.
FAU - Lambert, W Marcus
AU  - Lambert WM
AD  - Departments of Microbiology, New York University School of Medicine, New York, 
      New York, USA.
FAU - Xu, Chong-Feng
AU  - Xu CF
FAU - Neubert, Thomas A
AU  - Neubert TA
FAU - Chao, Moses V
AU  - Chao MV
FAU - Garabedian, Michael J
AU  - Garabedian MJ
FAU - Jeanneteau, Freddy D
AU  - Jeanneteau FD
LA  - eng
GR  - MH086651/MH/NIMH NIH HHS/United States
GR  - NS21072/NS/NINDS NIH HHS/United States
GR  - R01 NS021072/NS/NINDS NIH HHS/United States
GR  - 5T32AI07180-29/AI/NIAID NIH HHS/United States
GR  - P30 NS050276/NS/NINDS NIH HHS/United States
GR  - T32 AI007180/AI/NIAID NIH HHS/United States
GR  - R01 MH086651/MH/NIMH NIH HHS/United States
GR  - R56 NS021072/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130722
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Glucocorticoids)
RN  - 0 (Receptors, Glucocorticoid)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
EIN - Mol Cell Biol. 2013 Oct;33(20):4138
MH  - Animals
MH  - Biological Evolution
MH  - Brain-Derived Neurotrophic Factor/deficiency/genetics/*metabolism
MH  - Cells, Cultured
MH  - Conserved Sequence
MH  - Cyclic AMP Response Element-Binding Protein/metabolism
MH  - Dexamethasone/pharmacology
MH  - Glucocorticoids/genetics/*metabolism
MH  - HEK293 Cells
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mutagenesis, Site-Directed
MH  - Neurons/metabolism
MH  - Phosphorylation
MH  - Promoter Regions, Genetic
MH  - Rats
MH  - Receptor, trkB/deficiency/genetics/metabolism
MH  - Receptors, Glucocorticoid/deficiency/genetics/*metabolism
MH  - Signal Transduction
MH  - Transcriptome
PMC - PMC3753865
EDAT- 2013/07/24 06:00
MHDA- 2013/12/16 06:00
PMCR- 2014/03/01
CRDT- 2013/07/24 06:00
PHST- 2013/07/24 06:00 [entrez]
PHST- 2013/07/24 06:00 [pubmed]
PHST- 2013/12/16 06:00 [medline]
PHST- 2014/03/01 00:00 [pmc-release]
AID - MCB.00150-13 [pii]
AID - 00150-13 [pii]
AID - 10.1128/MCB.00150-13 [doi]
PST - ppublish
SO  - Mol Cell Biol. 2013 Sep;33(18):3700-14. doi: 10.1128/MCB.00150-13. Epub 2013 Jul 
      22.