PMID- 10406459
OWN - NLM
STAT- MEDLINE
DCOM- 19990921
LR  - 20180815
IS  - 0888-8809 (Print)
IS  - 0888-8809 (Linking)
VI  - 13
IP  - 7
DP  - 1999 Jul
TI  - A dominant role for the Raf-MEK pathway in forskolin, 12-O-tetradecanoyl-phorbol 
      acetate, and platelet-derived growth factor-induced CREB (cAMP-responsive
      element-binding protein) activation, uncoupled from serine 133 phosphorylation in
      NIH 3T3 cells.
PG  - 1071-83
AB  - In this study we describe that platelet-derived growth factor (PDGF),
      12-O-tetradecanoyl-phorbol-acetate (TPA), and forskolin induced CREB
      (cAMP-responsive element-binding protein) Ser-133 phosphorylation with comparable
      magnitude and kinetics in NIH 3T3 cells. While forskolin was the most potent
      activator of CREB, TPA or PDGF modestly increased CREB activity. The role of
      protein kinase C, protein kinase A, and the Raf-MEK kinase pathway in the
      activation and Ser-133 phosphorylation of CREB by these three stimuli was
      investigated. We found that inhibition of the Raf-MEK kinase pathway efficiently 
      blocks transcriptional activation of CREB by all three stimuli. This dominant
      involvement of Raf-MEK in CREB transcriptional activation seems to be uncoupled
      from CREB Ser-133 phosphorylation. We further demonstrate that although
      inhibition of Raf-MEK represses forskolin-induced CREB activation, forskolin by
      itself failed to activate ERK1/2 and Elk-1 mediated transcription. These results 
      suggest that a basal level of Raf-MEK activity is necessary for both PDGF- and
      forskolin-induced CREB activation, independent of CREB Ser-133 phosphorylation.
FAU - Seternes, O M
AU  - Seternes OM
AD  - Department of Gene Biology, Institute of Medical Biology, University of Tromso,
      Norway.
FAU - Johansen, B
AU  - Johansen B
FAU - Moens, U
AU  - Moens U
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Endocrinol
JT  - Molecular endocrinology (Baltimore, Md.)
JID - 8801431
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Elk1 protein, mouse)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Flavonoids)
RN  - 0 (Immediate-Early Proteins)
RN  - 0 (Platelet-Derived Growth Factor)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Transcription Factors)
RN  - 0 (ets-Domain Protein Elk-1)
RN  - 1F7A44V6OU (Colforsin)
RN  - 452VLY9402 (Serine)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-raf)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.25 (MAP Kinase Kinase Kinase 1)
RN  - EC 2.7.11.25 (Map3k1 protein, mouse)
RN  - EC 3.1.3.16 (Phosphoprotein Phosphatases)
RN  - EC 3.1.3.16 (Protein Phosphatase 1)
RN  - EC 3.1.3.48 (Dual Specificity Phosphatase 1)
RN  - EC 3.1.3.48 (Dual Specificity Phosphatase 6)
RN  - EC 3.1.3.48 (Dusp1 protein, mouse)
RN  - EC 3.1.3.48 (Dusp6 protein, mouse)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatases)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
SB  - IM
MH  - 3T3 Cells/drug effects/metabolism
MH  - Amino Acid Sequence
MH  - Animals
MH  - Calcium-Calmodulin-Dependent Protein Kinases/drug effects/metabolism
MH  - *Cell Cycle Proteins
MH  - Colforsin/metabolism/pharmacology
MH  - Cyclic AMP Response Element-Binding Protein/drug effects/genetics/*metabolism
MH  - Cyclic AMP-Dependent Protein Kinases/drug effects/metabolism
MH  - *DNA-Binding Proteins
MH  - Dual Specificity Phosphatase 1
MH  - Dual Specificity Phosphatase 6
MH  - Enzyme Activation/drug effects
MH  - Enzyme Inhibitors/pharmacology
MH  - Flavonoids/pharmacology
MH  - Immediate-Early Proteins/drug effects/genetics/metabolism
MH  - *MAP Kinase Kinase Kinase 1
MH  - Mice
MH  - Mitogen-Activated Protein Kinase 1
MH  - Mitogen-Activated Protein Kinase 3
MH  - *Mitogen-Activated Protein Kinases
MH  - Molecular Sequence Data
MH  - *Phosphoprotein Phosphatases
MH  - Phosphorylation
MH  - Platelet-Derived Growth Factor/metabolism/pharmacology
MH  - Protein Kinase C/drug effects/metabolism
MH  - Protein Phosphatase 1
MH  - Protein Tyrosine Phosphatases/drug effects/genetics/metabolism
MH  - Protein-Serine-Threonine Kinases/antagonists & inhibitors/*metabolism
MH  - Proto-Oncogene Proteins/drug effects/genetics/metabolism
MH  - Proto-Oncogene Proteins c-raf/metabolism
MH  - Serine/metabolism
MH  - Tetradecanoylphorbol Acetate/metabolism/pharmacology
MH  - *Transcription Factors
MH  - Transcriptional Activation
MH  - ets-Domain Protein Elk-1
EDAT- 1999/07/16 00:00
MHDA- 1999/07/16 00:01
CRDT- 1999/07/16 00:00
PHST- 1999/07/16 00:00 [pubmed]
PHST- 1999/07/16 00:01 [medline]
PHST- 1999/07/16 00:00 [entrez]
AID - 10.1210/mend.13.7.0293 [doi]
PST - ppublish
SO  - Mol Endocrinol. 1999 Jul;13(7):1071-83. doi: 10.1210/mend.13.7.0293.