CNK2 couples NGF signal propagation to multiple regulatory cascades driving cell differentiation
CNK2 couples NGF signal propagation to multiple regulatory cascades driving cell differentiation
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DOI：
10.1016/j.cub.2004.02.037
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发表时间：
2004-03-09
期刊：
影响因子：
9.2
通讯作者：
White, MA
中科院分区：
文献类型：
--
作者：
Bumeister, R;Rosse, C;White, MA
神经元前体细胞能够利用 Raf-MEK-ERK 信号模块来驱动两种截然不同的调节程序（增殖和分化）中的任意一种。这至少部分是激酶级联反应的刺激特异性形成的结果。例如，有丝分裂原 EGF 诱导短暂的 ERK 激活，而神经营养蛋白 NGF 则诱导延长的 ERK 激活 [1]。在这里，我们定义了调节机制的一个新组成部分，有助于 MAP 激酶信号传导与离散生物反应的选择性整合。我们发现支架/适配器蛋白 CNK2/MAGUIN-1 是 NGF 诱导的 ERK 激活所必需的，但 EGF 诱导的 ERK 激活则不需要。此外，CNK2 对 NGF 信号传导与膜/细胞骨架重塑的耦合做出了单独的重要贡献。我们认为 CNK2 整合了多种调控途径，这些途径必须协同作用才能驱动对外部刺激的适当生物反应。
Neuronal precursor cells have the capacity to engage the Raf-MEK-ERK signal module to drive either of two distinctly different regulatory programs, proliferation and differentiation. This is, at least in part, a consequence of stimulus-specific shaping of the kinase cascade response. For example, the mitogen EGF induces a transient ERK activation, whereas the neurotrophin NGF induces prolonged ERK activation [1]. Here we define a novel component of the regulatory machinery contributing to the selective integration of MAP kinase signaling with discrete biological responses. We show that the scaffold/adaptor protein CNK2/MAGUIN-1 is required for NGF- but not EGF-induced ERK activation. In addition, CNK2 makes a separate, essential contribution to the coupling of NGF signaling to membrane/ cytoskeletal remodeling. We propose that CNK2 integrates multiple regulatory pathways that must function in concert to drive an appropriate biological response to external stimuli.