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 cG MP-dependent protein kinase (PKG), regulates transcription of several genes , including immediate early genes. Using transfection experiments with the PKG-I alpha cDNA cloned from human aorta, we show here that addition of mem brane-permeable cGMP analogues to PC12 cells slightly upregulated ERK MAP ( mitogen-activated protein) kinase. Likewise, PKG-I alpha was found to activ ate weakly DNA binding activity of the Egr-1 transcription factor. On the o ther hand, PKG-I alpha overexpression was shown to tremendously amplify the Egr-1 binding activity induced by the neurotransmitter serotonin, which ac tivates egr-1 gene expression also via the stimulation of the ERK MAP kinas e pathway. Since this potentiation occurred neither at the level of ERK nor at the egr-1 transcriptional level, the mechanism of amplification probabl y results from the convergence of ERK and PKG pathways at the level of the transcription factor Egr-1. (C) 2001 Elsevier Science Inc. All rights reser ved.