Nitric oxide and cGMP regulate gene expression in neuronal and glial cellsby activating type II cGMP-dependent protein kinase

Nitric oxide (NO) and cGMP have been implicated in many neuronal functions, including regulation of gene expression, but little is known about the dow nstream targets of NO/cGMP in the nervous system, We found that type II cGM P-dependent protein kinase (G-kinase), which is widely expressed in the bra in, mediated NO- and cGMP-induced activation of the fos promoter in cells o f neuronal and glial origin; the enzyme was ineffective in regulating gene expression in fibroblast-like cells, The effect of G-kinase II on gene expr ession did not require calcium uptake but was synergistically enhanced by c alcium, G-kinase II was membrane associated and did not translocate to the nucleus; however, a soluble G-kinase II mutant translocated to the nucleus and regulated gene expression in fibroblast-like cells, Soluble G-kinase I also regulates fos promoter activity, but membrane targeting of G-kinase I prevented the enzyme from translocating to the nucleus and regulating trans cription in multiple cell types, including glioma cells; this suggests that cell type-specific factor(s) that mediate the transcriptional effects of e xtranuclear G-kinase II are not regulated by G-kinase I, Our results sugges t that G-kinase I and II control gene expression by different mechanisms an d that NO effects on neuronal plasticity may involve G-kinase II regulation of gene expression.