title: Dok5 is involved in the signaling pathway of neurotrophin-3 against TrkC-induced apoptosis.
abstract: TrkC is a dependence receptor and many reports have shown that neurotrophin-3 promotes cell survival by inhibiting TrkC-induced apoptosis in many cell lines. However, the identity of the adaptor protein involved in the NT-3/TrkC signaling pathway regulating cell death and survival remains unclear. The downstream of tyrosine kinase/docking protein (Dok) adaptor protein 5 is one substrate of the TrkC receptor. Because NT-3 and its receptor, TrkC, are strongly expressed by sensory neurons, we measured the expression of Dok5 and TrkC in the developing mouse spinal cord and dorsal root ganglia (DRG). We found that the number of cells positive for both Dok5 and TrkC decreases with DRG development. Immunoprecipitation and immunofluorescence staining showed that Dok5 interacted with TrkC and partially colocalized with TrkC in DRG neurons. In HEK293T cells, TrkC triggered apoptosis, but NT-3 prevented TrkC-induced apoptosis. Interestingly, siRNA knockdown of Dok5 expression partially prevented the protection of NT-3 against TrkC-induced apoptosis by regulating the activity of caspase-3. Taken together, we concluded that Dok5 is necessary for NT-3 signaling to block TrkC-induced apoptosis.
authors: The State Key Laboratory of Medical Molecular Biology, Department of Molecular Biology and Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, PR China.
authors: Yanfang
authors: Y
authors: Pan
authors: Jing
authors: J
authors: Zhang
authors: Wei
authors: W
authors: Liu
authors: Pengcheng
authors: P
authors: Shu
authors: Bin
authors: B
authors: Yin
authors: Jiangang
authors: J
authors: Yuan
authors: Boqin
authors: B
authors: Qiang
authors: Xiaozhong
authors: X
authors: Peng
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D004622:Embryo, Mammalian; D005727:Ganglia, Spinal / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D008813:Mice, Inbred ICR; D020933:Neurotrophin 3 / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D020812:Receptor, trkC / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C499010:Dok5 protein, mouse; D020933:Neurotrophin 3; D010750:Phosphoproteins; D020812:Receptor, trkC; D053148:Caspase 3
keywords: Apoptosis; Dok5; Dorsal root ganglia (DRG); NT-3; TrkC