Nitric oxide and cGMP regulate gene expression in neuronal and glial cells by 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 downstream targets of NO/cGMP in the nervous system. We found that type II cGMP-dependent protein kinase (G-kinase), which is widely expressed in the brain, mediated NO- and cGMP-induced activation of the fos promoter in cells of neuronal and glial origin; the enzyme was ineffective in regulating gene expression in fibroblast-like cells. The effect of G-kinase II on gene expression did not require calcium uptake but was synergistically enhanced by calcium. 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 transcription in multiple cell types, including glioma cells; this suggests that cell type-specific factor(s) that mediate the transcriptional effects of extranuclear G-kinase II are not regulated by G-kinase I. Our results suggest that G-kinase I and II control gene expression by different mechanisms and that NO effects on neuronal plasticity may involve G-kinase II regulation of gene expression.-Gudi, T., Hong, G. K.-P., Vaandrager, A. B., Lohmann, S. M., Pilz, R. B. Nitric oxide and cGMP regulate gene expression in neuronal and glial cells by activating type II cGMP-dependent protein kinase.
Gudi
T
T
University of California, San Diego, and Cancer Center, La Jolla, California 92093-0652, USA.
Hong
G K
GK
Vaandrager
A B
AB
Lohmann
S M
SM
Pilz
R B
RB
D016475:3T3 Cells; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D006224:Cricetinae; D006152:Cyclic GMP / Q000502:physiology*; D062965:Cyclic GMP-Dependent Protein Kinase Type I; D062967:Cyclic GMP-Dependent Protein Kinase Type II; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism*; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D051379:Mice; D009457:Neuroglia / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D016761:Oncogene Proteins v-fos / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000502:physiology; D015398:Signal Transduction; D015533:Transcriptional Activation
D016761:Oncogene Proteins v-fos; D009569:Nitric Oxide; D062965:Cyclic GMP-Dependent Protein Kinase Type I; D062967:Cyclic GMP-Dependent Protein Kinase Type II; D017869:Cyclic GMP-Dependent Protein Kinases; C569720:Prkg1 protein, mouse; C569730:Prkg2 protein, mouse; D006152:Cyclic GMP; D002118:Calcium