OPPOSING EFFECTS OF ERK AND JNK-P38 MAP KINASES ON APOPTOSIS
OPPOSING EFFECTS OF ERK AND JNK-P38 MAP KINASES ON APOPTOSIS
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DOI：
10.1126/science.270.5240.1326
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发表时间：
1995-11-24
期刊：
影响因子：
56.9
通讯作者：
GREENBERG, ME
中科院分区：
文献类型：
--
作者：
XIA, ZG;DICKENS, M;GREENBERG, ME
细胞凋亡在神经元发育过程中起着重要的作用，细胞凋亡的缺陷可能是各种神经退行性疾病的基础。为了研究调控神经元凋亡的分子机制，有丝分裂原活化蛋白激酶（mitogen-activated protein，MAP）家族成员，包括ERK，细胞外信号调节激酶在从大鼠PC-12嗜铬细胞瘤细胞中撤出神经生长因子（NGF）后，检测c-JUN NH 2-末端蛋白激酶（c-JUN NH 2-terminal protein kinase）和p38。NGF撤除导致JNK和p38酶的持续激活和ERK的抑制。JNK-p38和ERK信号传导途径的各种组分的显性干扰或组成性激活形式的作用表明，JNK和p38的激活和ERK的同时抑制对于这些细胞中诱导凋亡是至关重要的。因此，生长因子激活的ERK和应激激活的JNK-p38通路之间的动态平衡可能在决定细胞存活或凋亡方面很重要。
Apoptosis plays an important role during neuronal development, and defects in apoptosis may underlie various neurodegenerative disorders, To characterize molecular mechanisms that regulate neuronal apoptosis, the contributions to cell death of mitogen-activated protein (MAP) kinase family members, including ERK (extracellular signal-regulated kinase), JNK (c-JUN NH2-terminal protein kinase), and p38, were examined after withdrawal of nerve growth factor (NGF) from rat PC-12 pheochromocytoma cells. NGF withdrawal led to sustained activation of the JNK and p38 enzymes and inhibition of ERKs, The effects of dominant-interfering or constitutively activated forms of various components of the JNK-p38 and ERK signaling pathways demonstrated that activation of JNK and p38 and concurrent inhibition of ERK are critical for induction of apoptosis in these cells. Therefore, the dynamic balance between growth factor-activated ERK and stress-activated JNK-p38 pathways may be important in determining whether a cell survives or undergoes apoptosis.