Tso Prudence H, Morris Christina J, Yung Lisa Y, Ip Nancy Y, Wong Yung H
Department of Biochemistry, The Molecular Neuroscience Center, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
Neurochem Res. 2009 Jun;34(6):1101-12. doi: 10.1007/s11064-008-9880-9. Epub 2008 Nov 14.
Nerve growth factor (NGF)-mediated activation of mitogen-activated protein kinases (MAPK) is critical for differentiation and apoptosis of PC12 cells. Since NGF employs stress-activated c-Jun N-terminal kinase (JNK) to regulate both programmed cell death and neurite outgrowth of PC12 cells, we examined NGF-regulated JNK activity and the role of G(i/o) proteins. Induction of JNK phosphorylation by NGF occurred in a time- and dose-dependent manner and was partially inhibited by pertussis toxin (PTX). To discern the participation of various signaling intermediates, PC12 cells were treated with specific inhibitors prior to NGF challenge. NGF-elevated JNK activity was abolished by inhibitors of JNK, p38 MAPK, Src, JAK3 and MEK1/2. NGF-dependent JNK phosphorylation became insensitive to PTX treatment upon transient expressions of Galpha(z) or the PTX-resistant mutants of Galpha(i1-3) and Galpha(oA). Collectively, these studies indicate that NGF-dependent JNK activity may be mediated via G(i1-3) proteins, JAK3, Src, p38 MAPK and the MEK/ERK cascade.
神经生长因子（NGF）介导的丝裂原活化蛋白激酶（MAPK）激活对于PC12细胞的分化和凋亡至关重要。由于NGF利用应激激活的c-Jun氨基末端激酶（JNK）来调节PC12细胞的程序性细胞死亡和神经突生长，我们研究了NGF调节的JNK活性以及G(i/o)蛋白的作用。NGF诱导的JNK磷酸化呈时间和剂量依赖性，且部分被百日咳毒素（PTX）抑制。为了辨别各种信号中间体的参与情况，在NGF刺激之前用特异性抑制剂处理PC12细胞。JNK、p38 MAPK、Src、JAK3和MEK1/2的抑制剂消除了NGF升高的JNK活性。在瞬时表达Gα(z)或Gα(i1-3)和Gα(oA)的PTX抗性突变体后，NGF依赖性JNK磷酸化对PTX处理变得不敏感。总体而言，这些研究表明，NGF依赖性JNK活性可能通过G(i1-3)蛋白、JAK3、Src、p38 MAPK和MEK/ERK级联介导。
