Son H, Kim K O, Kim J S, Chang M Y, Lee S H, Lee Y S
Department of Biochemistry, Hanyang University College of Medicine, 17 Haengdang-dong, Sungdong-gu, 133-791, Seoul, South Korea.
Neurosci Lett. 2001 Jul 27;308(1):37-40. doi: 10.1016/s0304-3940(01)01984-x.
Although cAMP response element binding protein (CREB)- and extracellular-regulated protein kinase (ERK)-mediated pathways have been linked to each other in neuronal differentiation, involvement of these in hippocampal neuronal cell line has not been defined. Using an immortalized hippocampal cell line, HiB5, we have tried a pairing of forskolin with KCl depolarization, which acts as an ERK and CREB kinase activator in hippocampal neurons, to investigate if an activation of ERK and phosphorylation of CREB at the critical regulatory site, serine 133 might be coupled in differentiation. Differentiation toward a neuronal phenotype was synergistically and markedly increased by the pairing of forskolin and KCl depolarization. The synergistic effect was accompanied by an increase in phosphorylation of CREB Ser-133, but not phosphorylation of ERK, and was not inhibited by MEK inhibitor, PD98059. These findings indicate that phosphorylation of the transcriptional factor CREB may function to facilitate differentiation of HiB5 cells.
尽管环磷酸腺苷反应元件结合蛋白（CREB）介导的途径和细胞外调节蛋白激酶（ERK）介导的途径在神经元分化过程中相互关联，但它们在海马神经元细胞系中的作用尚未明确。我们使用永生化海马细胞系HiB5，尝试将福斯可林与氯化钾去极化相结合（氯化钾在海马神经元中作为ERK和CREB激酶激活剂），以研究ERK的激活与关键调节位点丝氨酸133处CREB的磷酸化在分化过程中是否存在关联。福斯可林与氯化钾去极化相结合可协同且显著地促进向神经元表型的分化。这种协同效应伴随着CREB丝氨酸133磷酸化的增加，但ERK的磷酸化并未增加，并且不受MEK抑制剂PD98059的抑制。这些发现表明转录因子CREB的磷酸化可能有助于促进HiB5细胞的分化。
