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(The FASEB Journal. 1999;13:2143-2152.)
© 1999 FASEB

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

TANIMA GUDI*, GREGORY K.-P. HONG*, ARIE B. VAANDRAGER{ddagger}, SUZANNE M. LOHMANN§ and RENATE B. PILZ*1

* University of California, San Diego, and Cancer Center, La Jolla, California 92093-0652, USA;
{ddagger} Erasmus University, 3000 DR Rotterdam, The Netherlands; and
§ Institut für Klinische Biochemie und Pathobiochemie, Medizinische Universitätsklinik, 97080 Würzburg, Germany

1Correspondence: Department of Medicine, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0652. E-mail: rpilz{at}ucsd.edu

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.


Key Words: NO/cGMP signaling • nervous system • fos promoter




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