Greenberg M E, Thompson M A, Sheng M
Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115.
J Physiol Paris. 1992;86(1-3):99-108. doi: 10.1016/s0928-4257(05)80013-0.
Cellular immediate early genes (IEGs) are a class of genes whose transcription is transiently activated within minutes of exposure of cells to a wide range of extracellular stimuli. In mature neurons IEG expression can be triggered by a variety of neutrotransmitters and neurotrophic factors. The IEGs, many of which encode transcription factors, are believed to control the physiological response of the cells to the initial stimulation event by activating secondary programs of gene expression. The mechanism by which membrane depolarization/Ca2+ influx trigger the activation of one IEG, c-fos, has been characterized in PC12 cells. In these cells, the cAMP response element-binding protein (CREB) functions as a Ca2+ regulated transcription factor. In addition, CREB is an in vitro substrate for several Ca2+ calmodulin-dependent protein kinases (CaM kinases). These results suggest a model whereby activation of voltage sensitive Ca2+ channels stimulates CaM kinase activation leading to CREB phosphorylation and c-fos transcriptional activation.
细胞即刻早期基因（IEGs）是一类基因，其转录在细胞暴露于多种细胞外刺激后的几分钟内被短暂激活。在成熟神经元中，IEG表达可由多种神经递质和神经营养因子触发。许多IEG编码转录因子，据信它们通过激活基因表达的次级程序来控制细胞对初始刺激事件的生理反应。膜去极化/Ca2+内流触发一种IEG即c-fos激活的机制已在PC12细胞中得到表征。在这些细胞中，cAMP反应元件结合蛋白（CREB）作为一种Ca2+调节的转录因子发挥作用。此外，CREB是几种Ca2+钙调蛋白依赖性蛋白激酶（CaM激酶）的体外底物。这些结果提示了一种模型，即电压敏感Ca2+通道的激活刺激CaM激酶的激活，导致CREB磷酸化和c-fos转录激活。
