CREB: A major mediator of neuronal neurotrophin responses

被引:780
作者
Finkbeiner, S
Tavazoie, SF
Maloratsky, A
Jacobs, KM
Harris, KM
Greenberg, ME
机构
[1] CHILDRENS HOSP, DEPT NEUROL, DIV NEUROSCI, BOSTON, MA 02115 USA
[2] HARVARD UNIV, SCH MED, GRAD PROGRAM NEUROSCI, BOSTON, MA 02115 USA
[3] HARVARD UNIV, SCH MED, DEPT NEUROBIOL, BOSTON, MA 02115 USA
关键词
D O I
10.1016/S0896-6273(00)80395-5
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Neurotrophins regulate neuronal survival, differentiation, and synaptic function. To understand how neurotrophins elicit such diverse responses, we elucidated signaling pathways by which brain-derived neurotrophic factor (BDNF) activates gene expression in cultured neurons and hippocampal slices. We found, unexpectedly, that the transcription factor cyclic AMP response element-binding protein (CREB) is an important regulator of BDNF-induced gene expression. Exposure of neurons to BDNF stimulates CREB phosphorylation and activation via at least two signaling pathways: by a calcium/calmodulin-dependent kinase IV (CaMKIV)-regulated pathway that is activated by the release of intracellular calcium and by a Ras-dependent pathway. These findings reveal a previously unrecognized, CaMK-dependent mechanism by which neurotrophins activate CREB and suggest that CREB plays a central role in mediating neurotrophin responses in neurons.
引用
收藏
页码:1031 / 1047
页数:17
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