Induction of the mitogen-activated protein kinase phosphatase MKP3 by nerve growth factor in differentiating PC12
Induction of the mitogen-activated protein kinase phosphatase MKP3 by nerve growth factor in differentiating PC12
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DOI：
10.1016/s0014-5793(98)00250-6
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发表时间：
1998-03-27
期刊：
影响因子：
3.5
通讯作者：
Arkinstall, S
中科院分区：
文献类型：
--
作者：
Camps, M;Chabert, C;Arkinstall, S
在 PC12 中，ERK 家族 MAP 激酶的交感神经元激活和核转位在神经生长因子 (NGF) 依赖性分化的过程中发挥着重要作用。我们最近克隆了 MKP-3 作为一种新型双特异性磷酸酶，对 ERK1 和 ERK2 MAP 激酶的失活具有选择性。在这里，我们报道，在 PC12 细胞中，MKP-3 受到 NGF 的强大而特异性的上调，而许多有丝分裂原和细胞应激则无效。 NGF 刺激的 MKP-3 表达在 1 小时后出现，在 3 小时时达到最大，并持续 5 天。这与神经突生长和终末分化的关键时期一致。与介导 PC12 细胞 MAP 激酶抑制的作用一致，在用成纤维细胞生长因子和 9-顺式视黄醛（发现另外两种分化因子）预处理后，NGF 刺激的 ERK2 激活被显着抑制，这两种因子被发现能强烈诱导 MKP-3 表达。鉴于 MKP3 在 PC12 细胞和交感神经元中明确的胞质定位，这些结果表明在 NGF 介导的 PC12 分化的关键阶段，非核区室中 ERK MAP 激酶的失活发挥着关键作用。 (C) 1998 年欧洲生化学会联合会。
In PC12 sympathetic neurons activation and nuclear translocation of ERK family MAP kinases plays an essential role in processes underlying nerve growth factor (NGF)-dependent differentiation. We have recently cloned MKP-3 as a novel dual specificity phosphatase displaying selectivity towards inactivation of the ERK1 and ERK2 MAP kinases. Here we report that in PC12 cells, MKP-3 undergoes powerful and specific up-regulation by NGF while a number of mitogens and cellular stresses are ineffective. NGF-stimulated MKP-3 expression appears after 1 h, is maximal at 3 h, and is sustained for 5 days. This coincides with a critical period of neurite outgrowth and terminal differentiation. Consistent with a role mediating inhibition of PC12 cell MAP kinases, NGF-stimulated ERK2 activation was suppressed considerably following pretreatment with fibroblast growth factor and 9-cis-retinal, two additional differentiation factors found to induce powerfully MKP-3 expression. Given the clear cytosolic localization of MKP3 in PC12 cells and sympathetic neurons, these results suggest a critical role for inactivating ERK MAP kinases in nonnuclear compartments during essential stages of NGF-mediated PC12 differentiation. (C) 1998 Federation of European Biochemical Societies.