Regulation of neuronal survival by the extracellular signal-regulated protein kinase 5.
Regulation of neuronal survival by the extracellular signal-regulated protein kinase 5.
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通过细胞外信号调节的蛋白激酶5来调节神经元存活。
DOI：
10.1038/cdd.2008.193
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发表时间：
2009-05
影响因子：
12.4
通讯作者：
Tournier, C.
中科院分区：
文献类型：
--
作者：
Finegan, K. G.;Wang, X.;Lee, E-J;Robinson, A. C.;Tournier, C.
细胞外信号调节蛋白激酶5 （ERK5）是一种丝裂原活化蛋白激酶（MAPK），它磷酸化并调节各种转录因子，以响应生长因子和细胞外应激。为了解决其在周围神经系统（PNS）发育过程中的生物学功能，我们设计了一种新的交感神经元模型，其中erk5基因可以在体外删除。我们的数据首次提供了ERK5介导神经元对神经生长因子（NGF）的生存反应的遗传证据。与ERK5缺失相关的细胞死亡增加是由Bcl-2家族中仅bh3成员、Bad和Bim的表达升高引起的。进一步研究发现，ERK5分别通过Ca++/cAMP反应元件结合蛋白（CREB）和叉头盒03a （Foxo3a）抑制bad和bim基因的转录。我们一致发现，在缺乏ERK5的神经元中，p90核糖体S6激酶（RSK）和蛋白激酶B （PKB）的磷酸化都受到损害。这些发现揭示了一种新的信号机制，在PNS发育过程中促进神经元存活。
The extracellular signal-regulated protein kinase 5 (ERK5) is a mitogen-activated protein kinase (MAPK) that phosphorylates and regulates various transcription factors in response to growth factors and extra-cellular stresses. To address its biological function during the development of the peripheral nervous system (PNS), we have engineered a novel model of sympathetic neurons in which the erk5 gene can be deleted in vitro. Our data provide for the first time genetic evidence that ERK5 is required to mediate the survival response of neurons to nerve growth factor (NGF). Increased cell death associated with the loss of ERK5 is caused by elevated expression of the BH3-only members of the Bcl-2 family, Bad and Bim. Further investigation indicated that ERK5 suppresses the transcription of the bad and the bim genes via Ca++/cAMP response element binding protein (CREB) and Forkhead box 03a (Foxo3a), respectively. Consistently, we found that the phosphorylation of both p90 ribosomal S6 kinase (RSK) and protein kinase B (PKB) is impaired in neurons lacking ERK5. Together these findings reveal a novel signaling mechanism that promotes neuronal survival during the development of the PNS.
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影响因子：
64.5
作者：
Brunet, A;Bonni, A;Greenberg, ME
通讯作者：
Greenberg, ME
影响因子：
14.9
作者：
Liu, YZ;Boxer, LM;Latchman, DS
通讯作者：
Latchman, DS
影响因子：
16.2
作者：
Putcha, GV;Le, SY;Johnson, EM
通讯作者：
Johnson, EM
FOXO转录因子直接激活BIM基因表达并促进交感神经元中的凋亡。
影响因子：
7.8
作者：
Gilley, Jonathan;Coffer, Paul J;Ham, Jonathan
通讯作者：
Ham, Jonathan
影响因子：
4.8
作者：
Creedon, DJ;Johnson, EM;Lawrence, JC
通讯作者：
Lawrence, JC