Individual and Combined Effects of TrkA and p75NTR Nerve Growth Factor Receptors
Individual and Combined Effects of TrkA and p75NTR Nerve Growth Factor Receptors
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TrkA 和 p75NTR 神经生长因子受体的单独和联合作用
DOI：
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发表时间：
2003
影响因子：
4.8
通讯作者：
K. Neet
中科院分区：
文献类型：
--
作者：
S. Lad;D. Peterson;R. Bradshaw;K. Neet
神经营养因子信号转导中的一个长期存在的问题是异聚TrkA-p75 NTR复合物是否具有与单独的同源寡聚TrkA或p75 NTR显著不同的信号传导能力。为了解决这个问题，表达血小板衍生生长因子受体-TrkA嵌合体和p75 NTR选择性神经生长因子突变体（Δ9/13 NGF）的转染PC 12细胞的各种组合分别用于选择性刺激TrkA或p75 NTR信号传导。在下游信号传导和某些终点方面分析了单个和组合受体效应的贡献。结果表明，高亲和力异聚体NGF受体位点的两个独特功能：（a）在NGF诱导的神经突生长的产生中整合MAPK和Akt途径，以及（B）Akt途径的快速和持续激活，从而导致细胞长期存活。TrkA信号传导的激活足以引发PC 12细胞中的神经突生长，而通过p75 NTR的信号传导则发挥着调节作用，特别是在增加精细突触“纽扣样”结构的形成方面，其中TrkA和p75 NTR似乎共定位。此外，TrkA/p75 NTR异聚体受体信号转导网络中的一种新的相互作用被揭示，即NGF诱导的MAPK通路的激活似乎抑制了平行的NGF诱导的Akt通路。
A long-standing question in neurotrophin signal transduction is whether heteromeric TrkA-p75NTR complexes possess signaling capabilities that are significantly different from homo-oligomeric TrkA or p75NTR alone. To address this issue, various combinations of transfected PC12 cells expressing a platelet-derived growth factor receptor-TrkA chimera and the p75NTR-selective nerve growth factor mutant (Δ9/13 NGF) were utilized to selectively stimulate TrkA or p75NTR signaling, respectively. The contribution of individual and combined receptor effects was analyzed in terms of downstream signaling and certain end points. The results suggest two unique functions for the high affinity heteromeric NGF receptor site: (a) integration of both the MAPK and Akt pathways in the production of NGF-induced neurite outgrowth, and (b) rapid and sustained activation of the Akt pathway, with consequent long term cellular survival. Whereas activation of TrkA signaling is sufficient for eliciting neurite outgrowth in PC12 cells, signaling through p75NTR plays a modulatory role, especially in the increased formation of fine, synaptic “bouton-like” structures, in which both TrkA and p75NTR appear to co-localize. In addition, a new interaction in the TrkA/p75NTR heteromeric receptor signal transduction network was revealed, namely that NGF-induced activation of the MAPK pathway appears to inhibit the parallel NGF-induced Akt pathway.
PC12 细胞中蛋白激酶 C 在神经突延伸和神经生长因子诱导鸟氨酸脱羧酶中缺乏作用。
DOI：
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发表时间：
1989
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Reinhold,DS;Neet,KE
通讯作者：
Neet,KE
重组β神经生长因子未加工的C端二肽决定了具有不同生物活性的三种稳定形式。
DOI：
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发表时间：
1992
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Luo,Y;Neet,KE
通讯作者：
Neet,KE
TrkA 的移动性通过磷酸化以及与低亲和力 NGF 受体的相互作用来调节。
DOI：
10.1021/bi9719253
发表时间：
1998
期刊：
Biochemistry.
影响因子：
--
作者：
Wolf,DE;McKinnon-Thompson,C;Daou,MC;Stephens,RM;Kaplan,DR;Ross,AH
通讯作者：
Ross,AH