Agonist antibody activates death receptor 6 downstream signaling involving TRADD recruitment |
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Authors: | Rui Hu Qiumei Du Xiangyun Yin Jingyun Li Tingting Wang Liguo Zhang |
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Affiliation: | 1. CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China;2. University of Chinese Academy of Sciences, Beijing 100049, China;3. Department of Neurology, General Hospital of PLA Shenyang Military Area Command, Shenyang 110015, China |
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Abstract: | Death receptor 6 (DR6) is a member of the death domain-containing receptors that belong to the TNFR superfamily. To date, the ligand for DR6 is still not clearly defined. Here, we developed a functional agonist monoclonal antibody (DQM3) against DR6, which bound to the first cysteine-rich domain. Importantly, DR6 signaling could be clearly activated by DQM3, which was dependent on its intracellular death domain. In addition, we demonstrated that the association between DR6 and TRADD was enhanced upon DQM3 stimulation and TRADD was involved in DR6-induced signaling activation. Taken together, our findings provide new insight into a novel mechanism by which DR6 induces downstream signaling in response to an agonist antibody. |
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Keywords: | CRD, cysteine-rich domain DD, death domain DR, death receptor FADD, Fas-associated death domain JNK, c-Jun N-terminal kinase N-APP, N-terminal β-amyloid precursor protein siRNA, small interfering RNA TNFR, tumor necrosis factor receptor TRADD, TNFR-associated death domain protein TRAF, tumor necrosis factor receptor-associated factor |
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