Marchi Matilde, Parra Riccardo, Costa Mario, Ratto Gian Michele
NEST/INFM and Scuola Normale Superiore, Pisa, Italy.
Methods Mol Biol. 2010;661:287-301. doi: 10.1007/978-1-60761-795-2_17.
The action of ERK1 and ERK2 activity on the nuclear substrates requires crossing the nuclear envelope and the localization of phospho-ERK into the nucleus. The nucleo-cytoplasmic trafficking of ERK is therefore crucial for the correct functioning of the pathway. Indeed, this step is necessary for the correct control of gene expression by growth-factors, for morphological transformation of fibroblasts and for neurite extension in PC12. Furthermore, disruption of ERK2 localization in the nucleus severely affects the transduction of ERK2 signaling. This process has now been observed and quantitatively measured by expressing fluorescently tagged ERK1 and ERK2. These experiments provide important insight on the operation of these signaling modules and have revealed an hitherto unknown functional difference between ERK1 and ERK2.
ERK1和ERK2活性作用于核底物需要穿过核膜并使磷酸化ERK定位于细胞核内。因此，ERK的核质转运对于该信号通路的正常功能至关重要。实际上，这一步骤对于生长因子正确调控基因表达、成纤维细胞的形态转化以及PC12细胞中的神经突延伸都是必需的。此外，ERK2在细胞核内定位的破坏会严重影响ERK2信号的转导。现在通过表达荧光标记的ERK1和ERK2已观察到并定量测量了这一过程。这些实验为这些信号模块的运作提供了重要的见解，并揭示了ERK1和ERK2之间迄今未知的功能差异。
