Article (Scientific journals)
Inhibition of protein phosphatase PP1 in GH3B6, but not in GH3 cells, activates the MEK/ERK/c-fos pathway and the human prolactin promoter, involving the coactivator CPB/p300
Manfroid, Isabelle; Martial, Joseph; Muller, Marc
2001In Molecular Endocrinology, 15 (4), p. 625-37
Peer Reviewed verified by ORBi
 

Files


Full Text
Inhibition of protein phosphatase PP1 in GH3B6 but not in GH3 cells.pdf
Publisher postprint (358.19 kB)
Request a copy

2001/03/27


All documents in ORBi are protected by a user license.

Send to



Details



Keywords :
Animals; DNA-Binding Proteins/genetics/metabolism; E1A-Associated p300 Protein; Enzyme Inhibitors/pharmacology; Flavonoids/pharmacology; Humans; Isoenzymes; *MAP Kinase Kinase Kinase 1; Mitogen-Activated Protein Kinases/antagonists & inhibitors/*metabolism; Nuclear Proteins/*metabolism; Okadaic Acid/pharmacology; Phosphoprotein Phosphatases/*antagonists & inhibitors/genetics/metabolism; Pituitary Neoplasms; Prolactin/*genetics/metabolism; Promoter Regions, Genetic; Protein-Serine-Threonine Kinases/metabolism; Proto-Oncogene Proteins c-fos/drug effects/*genetics/metabolism; Rats; Signal Transduction; Trans-Activators/*metabolism; Transcription Factor AP-1/genetics/metabolism; Transcription Factor Pit-1; Transcription Factors/genetics/metabolism; Transcriptional Activation; Tumor Cells, Cultured; ras Proteins/drug effects/genetics/metabolism
Abstract :
[en] The human (hPRL) PRL gene proximal promoter (-164/+15) is the target for numerous signal transduction pathways involving protein kinases. The inhibitor of Ser/Thr-protein phosphatases okadaic acid (OA) was shown to induce this promoter in rat pituitary GH3B6 through a synergism between increased amounts of the ubiquitous factor AP-1 and the pituitary-specific factor Pit-1. Here we show that this activation results mainly from transcriptional stimulation of the c-fos promoter leading to increased AP-1 activity. We report the surprising absence of the hPRL and c-fos promoter stimulation by OA in GH3 cells, closely related to GH3B6 cells, and we use this discrepancy to dissect the precise mechanism of action. c-fos gene activation involves the mitogen-activated kinase (MAPK)-ternary complex factor (TCF) pathway and can be obtained by expressing active V12ras in both cell lines. We show that OA acts by inhibiting protein phosphatase PP1, thereby protecting MAPK kinase (MEK)1/2 and/or a MEK1/2-kinase from dephosphorylation. PP1 inhibition of MEK activation by V12ras does not occur in GH3 cells, indicating that a distinct, PP1-sensitive phosphorylation site is used in GH3B6 cells to activate the TCF pathway in GH3B6 cells. Finally, we show that the synergistic OA activation of the hPRL promoter by Pit-1 and AP-1 is independent of the Pit-1 transactivation domain and is mediated by the general coactivator (CRE-binding protein)-binding protein (CBP)/p300.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Manfroid, Isabelle ;  Université de Liège - ULiège > GIGA-Research
Martial, Joseph ;  Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire
Muller, Marc  ;  Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire
Language :
English
Title :
Inhibition of protein phosphatase PP1 in GH3B6, but not in GH3 cells, activates the MEK/ERK/c-fos pathway and the human prolactin promoter, involving the coactivator CPB/p300
Publication date :
2001
Journal title :
Molecular Endocrinology
ISSN :
0888-8809
eISSN :
1944-9917
Publisher :
Endocrine Society, Chevy Chase, United States - Maryland
Volume :
15
Issue :
4
Pages :
625-37
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 04 December 2009

Statistics


Number of views
35 (3 by ULiège)
Number of downloads
1 (1 by ULiège)

Scopus citations®
 
19
Scopus citations®
without self-citations
16
OpenCitations
 
12

Bibliography


Similar publications



Contact ORBi