Amyloid precursor protein modulates the interaction of nerve growth factor with p75 receptor and potentiates its activation of trkA phosphorylation
Amyloid precursor protein modulates the interaction of nerve growth factor with p75 receptor and potentiates its activation of trkA phosphorylation
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DOI：
10.1016/s0169-328x(98)00037-0
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发表时间：
1998-05-01
期刊：
影响因子：
--
通讯作者：
Wallace, WC
中科院分区：
文献类型：
--
作者：
Akar, CA;Wallace, WC
我们最近发现淀粉样前体蛋白（APP）的分泌形式增强了神经生长因子（NGF）的神经营养作用。低浓度的NGF和APP的组合存在导致对PC 12细胞的NGF神经突发生活性的协同增强。因此，APP对NGF受体结合的影响已经被检查。在APP的存在下，NGF的低亲和力结合位点的表观亲和力增加了2. 5倍。此外，观察到位点数量减少2- 2.5倍，尽管APP不与NGF竞争相同的结合位点。APP的这些作用不是由与NGF本身的直接相互作用引起的。此外，APP（s）协同增强了由NGF引起的trkA的酪氨酸磷酸化。这些结果表明，增加的p75对NGF的亲和力可能是APP（s）增强NGF的神经营养作用的基础，这种增加可能是由APP（s）和p75之间的间接相互作用引起的。(C)1998年Elsevier Science B.V.
We have recently shown that the secreted form of amyloid precursor protein (APP(s)) potentiates the neurotrophic actions of nerve growth factor (NGF). The combined presence of NGF and APP(s) in low concentrations resulted in a synergistic potentiation of NGF neuritogenic activity on PC12 cells. Therefore, the effect of APP(s) on NGF receptor-binding has been examined. In the presence of APP(s), the apparent affinity of NGF' s low affinity binding site increased by a factor of 2.5. In addition, a 2- to 2.5-fold decrease in the number of sites was observed, although APP(s) did not compete with NGF for the same binding sites. These effects of APP(s) were not caused by direct interaction with NGF itself. In addition, APP(s) synergistically potentiated the tyrosine phosphorylation of trkA due to NGF. These results suggest that an increased affinity of p75 for NGF may underlie the potentiation of neurotrophic actions of NGF by APP(s), and that increase may be caused by an indirect interaction between APP(s) and p75. (C) 1998 Elsevier Science B.V.