The TrkB-Shc site signals neuronal survival and local axon growth via MEK and PI3-kinase
The TrkB-Shc site signals neuronal survival and local axon growth via MEK and PI3-kinase
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DOI：
10.1016/s0896-6273(00)00035-0
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发表时间：
2000-08-01
期刊：
影响因子：
16.2
通讯作者：
Kaplan, DR
中科院分区：
文献类型：
--
作者：
Atwal, JK;Massie, B;Kaplan, DR
为了确定Trk发出的信号如何在初级神经元中传递神经营养因子作用，我们测试了TrkB在特定的效应器结合部位突变促进交感神经元存活或局部轴突生长的能力。TrkB以类似于TrkA的方式刺激信号蛋白并诱导生存和生长。与野生型TrkB相比，在Shc结合位点突变的TrkB对存活和生长的支持作用较差，而在PLC-Gamma 1结合位点突变的TrkB对生长和存活的支持作用较好。TrkB介导的神经元存活依赖于PI3-K活性，在较小程度上依赖于MEK活性，而生长依赖于MEK和PI3-K活性。这些结果表明，TrkB-Shc位点通过激活PI3-激酶和MEK信号通路调节神经元存活和轴突生长。
To determine how signals emanating from Trk transmit neurotrophin actions in primary neurons, we tested the ability of TrkB mutated at defined effector binding sites to promote sympathetic neuron survival or local axon growth. TrkB stimulated signaling proteins and induced survival and growth in a manner similar to TrkA. TrkB mutated at the Shc binding site supported survival and growth poorly relative to wild-type TrkB, whereas TrkB mutated at the PLC-gamma 1 binding site supported growth and survival well. TrkB-mediated neuronal survival was dependent on PI3-kinase and to a lesser extent MEK activity, while growth depended upon both MEK and PI3-kinase activities. These results indicate that the TrkB-Shc site mediates both neuronal survival and axonal outgrowth by activating the PI3-kinase and MEK signaling pathways.