Morgan J I, Curran T
Department of Neuroscience, Roche Institute of Molecular Biology, Roche Research Center, Nutley, New Jersey.
Cell Calcium. 1988 Dec;9(5-6):303-11. doi: 10.1016/0143-4160(88)90011-5.
Increases in intraneuronal free calcium result in the rapid, transient, induction of the fos and jun proto-oncogenes. In PC12 cells, induction may be elicited either by membrane depolarization or by direct activation of voltage-dependent calcium channels with BAY K 8644 both of which provoke an influx of calcium. The calmodulin pathway appears to link the elevated intracellular calcium to gene induction. In the brain, c-fos and c-jun may be induced by elevated neuronal activity such as occurs during pentylenetetrazole (PTZ) seizures. The N-methyl-D-aspartate (NMDA) form of the glutamate receptor, which can directly gate calcium, plays a role in the induction of c-fos expression in PTZ seizures. In addition, NMDA can directly stimulate c-fos in the brain. Fos and Jun form a noncovalent nucleoprotein complex that binds to the consensus recognition sequence of the AP-1 transcription factor. Thus in a larger picture we envisage Fos and Jun as members of a concerted stimulus-transcription coupling pathway that links alterations in external stimuli to long term adaptive responses. In this context Fos, Jun and the other immediate-early genes should be viewed as third messengers which are regulated by second messengers such as intracellular calcium.
神经元内游离钙的增加会导致原癌基因fos和jun的快速、短暂诱导。在PC12细胞中，膜去极化或用BAY K 8644直接激活电压依赖性钙通道均可引发诱导，这两种方式都会引起钙内流。钙调蛋白途径似乎将细胞内钙升高与基因诱导联系起来。在大脑中，c-fos和c-jun可能由神经元活动增强诱导产生，比如在戊四氮（PTZ）癫痫发作期间。谷氨酸受体的N-甲基-D-天冬氨酸（NMDA）亚型可直接控制钙通道，在PTZ癫痫发作时c-fos表达的诱导中发挥作用。此外，NMDA可直接刺激大脑中的c-fos。Fos和Jun形成一种非共价核蛋白复合物，该复合物可与AP-1转录因子的共有识别序列结合。因此，从更宏观的角度来看，我们设想Fos和Jun是协同刺激-转录偶联途径的成员，该途径将外部刺激的变化与长期适应性反应联系起来。在这种情况下，Fos、Jun和其他即刻早期基因应被视为第三信使，它们受细胞内钙等第二信使的调控。
