A TrkA-selective, fast internalizing nerve growth factor-antibody complex induces trophic but not neuritogenic signals
A TrkA-selective, fast internalizing nerve growth factor-antibody complex induces trophic but not neuritogenic signals
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DOI：
10.1074/jbc.273.52.34933
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发表时间：
1998-12-25
影响因子：
4.8
通讯作者：
Neet, KE
中科院分区：
文献类型：
--
作者：
Saragovi, HU;Zheng, WH;Neet, KE
神经生长因子（NGF）是一种神经营养因子，其通过与TrkA和/或p75受体结合来诱导神经生和营养信号。我们报告了一个比较研究的结合，内化，和生物活性的神经生长因子与神经生长因子与抗神经生长因子单克隆抗体（单克隆抗体NGF 30），直接对C末端的神经生长因子。NGF mAb复合物不能有效结合p75，但以高亲和力结合TrkA。结合后，NGF mAb复合物比NGF更快地刺激内化，并且程度更大。与NGF诱导的激活相比，NGF mAb诱导的TrkA、Shc和MAPK的激活是短暂的;然而NGF和NGF mAb提供相同的营养反应。与此相反，NGF诱导Suc-1相关的神经营养激活蛋白磷酸化和神经突分化，但NGF单克隆抗体没有。因此，对于NGF.mAb观察到营养和神经突发生功能的绝对分离，表明神经营养因子的生物反应调节剂可以提供具有选定活性的配体。
Nerve growth factor (NGF) is a neurotrophin that induces neuritogenic and trophic signals by binding to TrkA and/or p75 receptors. We report a comparative study of the binding, internalization, and biological activity of NGF versus that of NGF in association with an anti-NGF monoclonal antibody (mAb NGF30), directed against the C termini of NGF. NGF mAb complexes do not bind p75 effectively but bind TrkA with high affinity. After binding, NGF mAb complexes stimulate internalization faster and to a larger degree than NGF. NGF.mAb-induced activation of TrkA, Shc, and MAPK is transient compared with NGF-induced activation; yet NGF and NGF mAb afford identical trophic responses. In contrast, NGF induces Suc-1-associated neurotrophic activating protein phosphorylation and neuritogenic differentiation, but NGF mAb does not. Thus, an absolute separation of trophic and neuritogenic function is seen for NGF.mAb, suggesting that biological response modifiers of neurotrophins can afford ligands with selected activities.