Hansen Thomas v O, Rehfeld Jens F, Nielsen Finn C
Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, DK-2100, Copenhagen, Denmark.
Neurosci Lett. 2003 Aug 14;347(1):57-61. doi: 10.1016/s0304-3940(03)00581-0.
In the present study, the effect of KCl-induced calcium influx on PC12 cell differentiation was examined. We show that KCl depolarization potentiates the effect of forskolin-induced neurite outgrowth of PC12 cells. The effects of KCl and forskolin were mediated via the protein kinase A (PKA) and the extracellular signal-regulated kinase (ERK) signaling pathways, since addition of the ERK kinase (MEK1) inhibitor PD98059 and the PKA inhibitor H89 inhibits neurite outgrowth. KCl depolarization and forskolin synergistically activate the ERK signaling pathway, but whereas KCl-mediated ERK activation depends on both PKA and MEK1, forskolin activates ERK in a PKA-independent manner. Finally, we find that KCl depolarization and forskolin both induce nuclear ERK2 translocation via a PKA- and MEK1-dependent pathway. The results demonstrate that PKA and ERK play a key role in KCl- and forskolin-induced neuronal differentiation by integration of signals from both pathways.
在本研究中，检测了氯化钾诱导的钙内流对PC12细胞分化的影响。我们发现，氯化钾去极化增强了福斯高林诱导的PC12细胞神经突生长的作用。氯化钾和福斯高林的作用是通过蛋白激酶A（PKA）和细胞外信号调节激酶（ERK）信号通路介导的，因为添加ERK激酶（MEK1）抑制剂PD98059和PKA抑制剂H89会抑制神经突生长。氯化钾去极化和福斯高林协同激活ERK信号通路，但氯化钾介导的ERK激活依赖于PKA和MEK1，而福斯高林以不依赖PKA的方式激活ERK。最后，我们发现氯化钾去极化和福斯高林均通过PKA和MEK1依赖的途径诱导核ERK2易位。结果表明，PKA和ERK通过整合来自两条途径的信号，在氯化钾和福斯高林诱导的神经元分化中起关键作用。
