Nitric oxide and cGMP regulate gene expression in neuronal and glial cells by activating type II cGMP-dependent protein kinase
Nitric oxide and cGMP regulate gene expression in neuronal and glial cells by activating type II cGMP-dependent protein kinase
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DOI：
10.1096/fasebj.13.15.2143
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发表时间：
1999-12-01
期刊：
影响因子：
4.8
通讯作者：
Pilz, RB
中科院分区：
文献类型：
--
作者：
Gudi, T;Hong, GKP;Pilz, RB
一氧化氮（NO）和环鸟苷酸（cGMP）参与了神经元的许多功能，包括基因表达的调控，但NO/cGMP在神经系统中的下游靶点却知之甚少。在脑中广泛表达的G激酶介导NO和cGMP诱导的神经元和神经胶质细胞中fos启动子的激活; G-激酶II对成纤维细胞样细胞基因表达的调节作用不需要钙离子的摄取，但可被钙离子协同增强，G-激酶II是膜结合的，不转运到细胞核;然而，可溶性G-激酶II突变体易位到细胞核并调节成纤维细胞样细胞中的基因表达，可溶性G-激酶I也调节fos启动子活性，但是G-激酶I的膜靶向阻止了该酶转移到细胞核并在多种细胞类型中调节转录，包括神经胶质瘤细胞;这表明介导细胞核G-激酶II转录作用的细胞类型特异性因子不受G-激酶I调节，我们的研究结果表明，G-激酶I和II通过不同的机制控制基因表达，NO对神经元可塑性的影响可能涉及G-激酶II调节基因表达。
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.