TrkA and mitogen-activated protein kinase phosphorylation are enhanced in sympathetic neurons lacking functional p75 neurotrophin receptor expression
TrkA and mitogen-activated protein kinase phosphorylation are enhanced in sympathetic neurons lacking functional p75 neurotrophin receptor expression
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DOI：
10.1111/j.0953-816x.2004.03381.x
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发表时间：
2004-05-01
影响因子：
3.4
通讯作者：
Kawaja, MD
中科院分区：
文献类型：
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作者：
Hannila, SS;Lawrance, GM;Kawaja, MD
本研究探讨了低效型 p75 神经营养蛋白受体 (p75NTR) 表达和高水平神经生长因子 (NGF) 对 trkA 磷酸化和 p44/42 丝裂原激活蛋白激酶 (MAPK) 下游激活的影响。来自出生后第 1 天 p75NTR 外显子 III 无效突变体 (p75(-/-)) 和 129/SvJ 小鼠的节后交感神经元在 50 ng/mL NGF 存在下进行培养，并通过蛋白质印迹进行分析。与 129/SvJ 神经元相比，p75(-/-) 神经元中磷酸化 trkA 的水平有所增加，并且这些较高的水平在持续暴露于 NGF 的情况下得以维持。 MAPK 在 p75(-/-) 神经元中的磷酸化程度也高于 129/SvJ 神经元，无论是在暴露于 NGF 的 10 分钟内还是在连续 NGF 治疗 5 天的情况下。这些数据为p75(-/-)神经元神经突生长增强的机制提供了新的见解，证明当p75NTR功能被破坏时，交感神经元中的trkA和MAPK信号传导增加。
This study examined the effects of hypomorphic p75 neurotrophin receptor (p75NTR) expression and high levels of nerve growth factor (NGF) on trkA phosphorylation and downstream activation of p44/42 mitogen-activated protein kinase (MAPK). Post-ganglionic sympathetic neurons from postnatal day 1 p75NTR exon III null mutant (p75(-/-)) and 129/SvJ mice were cultured in the presence of 50 ng/mL NGF and analysed by Western blotting. Levels of phosphorylated trkA are increased in p75(-/-) neurons compared with 129/SvJ neurons, and these higher levels are maintained with continuous exposure to NGF. MAPK is also phosphorylated to a greater extent in p75(-/-) neurons than in 129/SvJ neurons, both within 10 min of exposure to NGF, and with continuous NGF treatment for 5 days. These data provide new insight into the mechanism underlying enhanced neurite outgrowth in p75(-/-) neurons, demonstrating that trkA and MAPK signalling in sympathetic neurons are increased when p75NTR function is disrupted.