Mitogen-activated protein kinase-independent pathways mediate the effects of nerve growth factor and cAMP on neuronal survival
Mitogen-activated protein kinase-independent pathways mediate the effects of nerve growth factor and cAMP on neuronal survival
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DOI：
10.1074/jbc.271.34.20713
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发表时间：
1996-08-23
影响因子：
4.8
通讯作者：
Lawrence, JC
中科院分区：
文献类型：
--
作者：
Creedon, DJ;Johnson, EM;Lawrence, JC
丝裂原活化蛋白激酶（MAP激酶）信号通路的组成部分，包括Pas、Raf和MAP激酶，是神经生长因子（NGF）诱导的PC12细胞神经突生长所必需的。我们已经研究了这一途径在促进初级交感神经元存活中的作用，这些神经元在被剥夺NGF时死亡。NGF引起MAP激酶ERK-1和ERK-2亚型活性的快速和持续增加（约4倍）。PD 098059是一种MAP激酶激活抑制剂，可阻断NGF对两种激酶亚型的作用。然而，PD 098059并没有减弱NGF对神经元存活的影响，此外，MAP激酶活性并没有被chlorophenylthio-cAMP （cAMP的细胞渗透性类似物，在缺乏NGF的情况下支持神经元存活）增加。这些发现表明，无论是cAMP还是NGF对神经元存活的作用，都不需要激活MAP激酶。
Components of the mitogen-activated protein kinase (MAP kinase) signaling pathway, including Pas, Raf, and MAP kinase, are necessary for nerve growth factor (NGF)-induced neurite outgrowth in PC12 cells. We have investigated the role of this pathway in promoting survival of primary sympathetic neurons that die when deprived of NGF. NGF caused rapid and sustained increases (approximately 4-fold) in the activities of the ERK-1 and ERK-2 isoforms of MAP kinase. PD 098059, an inhibitor of MAP kinase kinase activation, blocked the effects of NGF on both kinase isoforms. However, PD 098059 did not attenuate the effects of NGF on neuronal survival, In addition, MAP kinase activity was not increased by chlorophenylthio-cAMP, a cell-permeable analog of cAMP that supports neuronal survival in the absence of NGF. These findings indicate that activation of MAP kinase is not required for the actions of either cAMP or NGF on neuronal survival.