Cyclic GMP-dependent protein kinase potentiates serotonin-induced Egr-1 binding activity in PC12 cells.
The NO/cyclic GMP (cGMP) signal transduction pathway, which involves the cGMP-dependent protein kinase (PKG), regulates transcription of several genes, including immediate early genes. Using transfection experiments with the PKG-Ialpha cDNA cloned from human aorta, we show here that addition of membrane-permeable cGMP analogues to PC12 cells slightly upregulated ERK MAP (mitogen-activated protein) kinase. Likewise, PKG-Ialpha was found to activate weakly DNA binding activity of the Egr-1 transcription factor. On the other hand, PKG-Ialpha overexpression was shown to tremendously amplify the Egr-1 binding activity induced by the neurotransmitter serotonin, which activates egr-1 gene expression also via the stimulation of the ERK MAP kinase pathway. Since this potentiation occurred neither at the level of ERK nor at the egr-1 transcriptional level, the mechanism of amplification probably results from the convergence of ERK and PKG pathways at the level of the transcription factor Egr-1.
Esteve
L
L
INSERM Unité U338, Centre de Neurochimie, 5, rue Blaise Pascal, Cedex 67084, Strasbourg, France.
Lutz
P
P
Thiriet
N
N
Revel
M
M
Aunis
D
D
Zwiller
J
J
D000818:Animals; D015152:Blotting, Northern; D002467:Cell Nucleus / Q000378:metabolism; D003001:Cloning, Molecular; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism*; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D051766:Early Growth Response Protein 1; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D017874:Immediate-Early Proteins; D015151:Immunoblotting; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016716:PC12 Cells; D010766:Phosphorylation; D011485:Protein Binding; D051381:Rats; D012701:Serotonin / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection; D015854:Up-Regulation
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D004791:Enzyme Inhibitors; D017874:Immediate-Early Proteins; D014157:Transcription Factors; D012701:Serotonin; D017869:Cyclic GMP-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases