PMID- 11283010
OWN - NLM
STAT- MEDLINE
DCOM- 20010719
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 276
IP  - 24
DP  - 2001 Jun 15
TI  - Autoregulation of cell-specific MAP kinase control of the tryptophan hydroxylase 
      promoter.
PG  - 21262-71
AB  - The neurotransmitter serotonin controls a wide range of biological systems, 
      including its own synthesis and release. As the rate-limiting enzyme in serotonin 
      biosynthesis, tryptophan hydroxylase (TPH) is a potential target for this 
      autoregulation. Using the serotonergic neuron-like CA77 cell line, we have 
      demonstrated that treatment with a 5-hydroxytryptamine autoreceptor agonist, CGS 
      12066A, can lower TPH mRNA levels and promoter activity. We reasoned that this 
      repression might involve inhibition of MAP kinases, since 5-HT1 receptors can 
      increase mitogen-activated protein (MAP) kinase phosphatase levels. To test this 
      hypothesis, we first showed that the TPH promoter can be activated 20-fold by 
      mitogen-activated extracellular-signal regulated kinase kinase kinase (MEKK), an 
      activator of MAP kinases. This activation was then blocked by CGS 12066A. The 
      maximal MAP kinase and CGS repression regulatory region was mapped to between 
      -149 and -45 base pairs upstream of the transcription start site. The activation 
      by MEKK appears to be cell-specific, because MEKK did not activate the TPH 
      promoter in nonneuronal cell lines. At least part, but not all, of the MAP kinase 
      responsiveness was mapped to an inverted CCAAT box that binds the transcription 
      factor NF-Y. These data suggest a model for the autoregulation of serotonin 
      biosynthesis by repression of MAP kinase stimulation of the TPH promoter.
FAU - Wood, J L
AU  - Wood JL
AD  - Genetics Ph.D. Program and Department of Physiology and Biophysics, University of 
      Iowa, Iowa City, Iowa 52242, USA.
FAU - Russo, A F
AU  - Russo AF
LA  - eng
GR  - DK 25295/DK/NIDDK NIH HHS/United States
GR  - HD 25969/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20010330
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Butadienes)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Imidazoles)
RN  - 0 (Nitriles)
RN  - 0 (Pyridines)
RN  - 0 (Quinoxalines)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Serotonin Receptor Agonists)
RN  - 0 (U 0126)
RN  - 109028-10-6 (CGS 12066B)
RN  - EC 1.13.12.- (Luciferases)
RN  - EC 1.14.16.4 (Tryptophan Hydroxylase)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - OU13V1EYWQ (SB 203580)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Butadienes/pharmacology
MH  - CHO Cells
MH  - Cell Line
MH  - Cricetinae
MH  - Enzyme Inhibitors/pharmacology
MH  - Enzyme Repression/drug effects
MH  - *Gene Expression Regulation, Enzymologic/drug effects
MH  - Genes, Reporter
MH  - Imidazoles/pharmacology
MH  - Kinetics
MH  - Luciferases/genetics
MH  - MAP Kinase Signaling System/physiology
MH  - Mitogen-Activated Protein Kinases/*metabolism
MH  - Models, Biological
MH  - Molecular Sequence Data
MH  - Neurons/cytology/enzymology
MH  - Nitriles/pharmacology
MH  - *Promoter Regions, Genetic/drug effects
MH  - Pyridines/pharmacology
MH  - Quinoxalines/pharmacology
MH  - Recombinant Proteins/analysis/biosynthesis
MH  - Serotonin Receptor Agonists/pharmacology
MH  - Transcription, Genetic/drug effects
MH  - Transfection
MH  - Tryptophan Hydroxylase/biosynthesis/*genetics
EDAT- 2001/04/03 10:00
MHDA- 2001/07/20 10:01
CRDT- 2001/04/03 10:00
PHST- 2001/04/03 10:00 [pubmed]
PHST- 2001/07/20 10:01 [medline]
PHST- 2001/04/03 10:00 [entrez]
AID - S0021-9258(20)78690-4 [pii]
AID - 10.1074/jbc.M007520200 [doi]
PST - ppublish
SO  - J Biol Chem. 2001 Jun 15;276(24):21262-71. doi: 10.1074/jbc.M007520200. Epub 2001 
      Mar 30.