Inhibition of p42 and p44 mitogen-activated protein kinase activity by PD48059 does not suppress nerve growth factor-induced survival of sympathetic neurones

被引:0
|
作者
Virdee, K [1 ]
Tolkovsky, AM [1 ]
机构
[1] UNIV CAMBRIDGE,DEPT BIOCHEM,CAMBRIDGE CB2 1QW,ENGLAND
基金
英国惠康基金;
关键词
cell death; apoptosis; p21; Ras; ciliary neurotrophic factor; leukemia inhibitory factor; cyclic AMP;
D O I
暂无
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Nerve growth factor (NGF) induces persistent p42 and p44 mitogen-activated protein kinase (MAPK) activity in sympathetic neurones in parallel to its survival-promoting activity. To investigate whether these MAPK activities are necessary for NGF-induced survival, we have inhibited NGF-stimulated p42/p44 MAPK activity over extended periods using the compound 2-(2'-amino-3'-methoxyphenyl)-oxanaphthalen-4-one (PD98059). Despite attaining up to 95% inhibition of p42/p44 MAPK activity in cultures treated with NGF and PD98059, neuronal survival is maintained undiminished, although a decrease in the density of the neuritic network is observed. Because p21Ras activity is essential for NGF-induced survival, we conclude that p21Ras-linked activities other than p42 and p44 MAPKs are responsible for mediating NGF-dependent survival of rat sympathetic neurones.
引用
收藏
页码:1801 / 1805
页数:5
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