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-Iα 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-Iα was found to activate weakly DNA binding activity of the Egr-1 transcription factor. On the other hand, PKG-Iα 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.