Department of Pharmacology and Therapeutics, Lady Davis Research Institute-Jewish General Hospital, McGill University, Montreal, Quebec, Canada.
Dev Neurobiol. 2010 Feb 15;70(3):150-64. doi: 10.1002/dneu.20776.
The D5 domain of TrkC receptors is a docking site for Neurotrophin-3 (NT-3), but other domains may be relevant for function or harmonizing signals with p75(NTR) coreceptors. We report a monoclonal antibody (mAb) 2B7 targeting the juxtamembrane domain of TrkC. mAb 2B7 binds to murine and human TrkC receptors and is a functional agonist that affords activation of TrkC, AKT, and MAPK. These signals result in cell survival but not in cellular differentiation. Monomeric 2B7 Fabs also affords cell survival. Binding of 2B7 mAb and 2B7 Fabs to TrkC are blocked by NT-3 in a dose-dependent manner but not by pro-NT-3. Expression of p75(NTR) coreceptors on the cell surface block the binding and function of mAb 2B7, whereas NT-3 binding and function are enhanced. mAb 2B7 defines a previously unknown neurotrophin receptor functional hot spot; that exclusively generates survival signals; that can be activated by non-dimeric ligands; and potentially unmasks a site for p75-TrkC interactions.
TrkC 受体的 D5 结构域是神经营养因子-3（NT-3）的对接位点，但其他结构域可能与功能或与 p75（NTR）共受体协调信号有关。我们报告了一种针对 TrkC 跨膜区的单克隆抗体（mAb）2B7。mAb 2B7 结合小鼠和人类的 TrkC 受体，是一种功能性激动剂，可激活 TrkC、AKT 和 MAPK。这些信号导致细胞存活，但不导致细胞分化。单体 2B7 Fab 也可促进细胞存活。2B7 mAb 和 2B7 Fab 与 TrkC 的结合可被 NT-3 以剂量依赖的方式阻断，但不能被 pro-NT-3 阻断。细胞表面表达的 p75（NTR）共受体可阻断 mAb 2B7 的结合和功能，而 NT-3 的结合和功能则增强。mAb 2B7 定义了一个以前未知的神经营养因子受体功能热点；该热点专门产生存活信号；可被非二聚配体激活；并可能揭示了 p75-TrkC 相互作用的位点。
