p75 Reduces TrkB Tyrosine Autophosphorylation in Response to Brain-derived Neurotrophic Factor and Neurotrophin 4/5*
p75 Reduces TrkB Tyrosine Autophosphorylation in Response to Brain-derived Neurotrophic Factor and Neurotrophin 4/5*
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DOI：
10.1074/jbc.m001641200
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发表时间：
2000-08
期刊：
影响因子：
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通讯作者：
J. Vesa;A. Krüttgen;E. Shooter
中科院分区：
文献类型：
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作者：
J. Vesa;A. Krüttgen;E. Shooter
神经营养因子通过两种不同的受体介导其信号：受体酪氨酸激酶家族，Trks和低亲和力泛神经营养因子受体p75。Trk受体显示出更有限的配体特异性，而所有神经营养因子都能够与p75结合。p75的一个重要功能是通过增加TrkA酪氨酸自磷酸化来增强神经生长因子经由TrkA的信号传导。在这里，我们已经研究了在MG 87成纤维细胞系稳定转染p75和TrkB或p75和TrkC，以及在PC 12细胞稳定转染TrkB的TrkB和TrkC介导的神经营养因子信号的重要性。与TrkA信号传导相反，p75对其同源神经营养因子、脑源性神经营养因子和神经营养因子4/5的反应对TrkB酪氨酸自磷酸化具有负面影响。另一方面，在神经营养因子3处理中，p75对TrkB或TrkC活化没有影响。p75不影响细胞外信号调节激酶2对脑源性神经营养因子、神经营养因子3或神经营养因子4/5的酪氨酸磷酸化。这些结果表明，在神经营养因子治疗中，观察到的由p75引起的TrkB酪氨酸自磷酸化的减少不影响Ras/促分裂原活化蛋白激酶信号通路。
Neurotrophins mediate their signals through two different receptors: the family of receptor tyrosine kinases, Trks, and the low affinity pan-neurotrophin receptor p75. Trk receptors show more restricted ligand specificity, whereas all neurotrophins are able to bind to p75. One important function of p75 is the enhancement of nerve growth factor signaling via TrkA by increasing TrkA tyrosine autophosphorylation. Here, we have examined the importance of p75 on TrkB- and TrkC-mediated neurotrophin signaling in an MG87 fibroblast cell line stably transfected with either p75 and TrkB or p75 and TrkC, as well as in PC12 cells stably transfected with TrkB. In contrast to TrkA signaling, p75 had a negative effect on TrkB tyrosine autophosphorylation in response to its cognate neurotrophins, brain-derived neurotrophic factor and neurotrophin 4/5. On the other hand, p75 had no effect on TrkB or TrkC activation in neurotrophin 3 treatment. p75 did not effect extracellular signal-regulated kinase 2 tyrosine phosphorylation in response to brain-derived neurotrophic factor, neurotrophin 3, or neurotrophin 4/5. These results suggest that the observed reduction in TrkB tyrosine autophosphorylation caused by p75 does not influence Ras/mitogen-activated protein kinase signaling pathway in neurotrophin treatments.