Liu F C, Graybiel A M
Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences, Cambridge 02139, USA.
Neuron. 1996 Dec;17(6):1133-44. doi: 10.1016/s0896-6273(00)80245-7.
The cAMP response element-binding protein (CREB) is a plasticity-associated transcription factor that can potentially integrate cAMP and calcium signals at the gene activation level. We tested for convergent Ser-133 phosphorylation of CREB via dopamine D1/D5 receptors and L-type calcium channels in organotypic cultures of neonatal striatum. We found such convergence only transiently. Sustained CREB phosphorylation by D1/D5 receptor and L-type channel agonists was targeted to opposite (striosome and matrix) cellular phenotypes. Subsequent expression of the CRE-containing gene, c-fos, matched the divergent patterns of sustained CREB phosphorylation, and both divergent patterns could be switched by inhibition of phosphatases, including calcineurin. Control of the duration of CREB phosphorylation may be a critical regulator of CRE-mediated gene expression by dopamine and calcium.
环磷酸腺苷反应元件结合蛋白（CREB）是一种与可塑性相关的转录因子，它有可能在基因激活水平整合环磷酸腺苷（cAMP）和钙信号。我们在新生纹状体的器官型培养物中，检测了通过多巴胺D1/D5受体和L型钙通道对CREB丝氨酸133位点的磷酸化是否存在汇聚现象。我们发现这种汇聚只是短暂的。D1/D5受体和L型通道激动剂对CREB的持续磷酸化作用针对的是相反的（纹状体小体和基质）细胞表型。随后含CRE的基因c-fos的表达与CREB持续磷酸化的不同模式相匹配，并且这两种不同模式都可以通过抑制包括钙调神经磷酸酶在内的磷酸酶来切换。对CREB磷酸化持续时间的控制可能是多巴胺和钙介导的CRE基因表达的关键调节因素。
