期刊
NATURE COMMUNICATIONS
卷 7, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms11686
关键词
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资金
- National Research Foundation of Korea [2013R1A1A2059911]
- Intelligent Synthetic Biology Center of the Global Frontier Project - Ministry of Education, Science and Technology [2013-0073185]
- Asan Institute for Life Sciences and Corporate Relations of Asan Medical Center, Seoul, Korea [15-515]
- National Research Foundation of Korea [2013R1A1A2059911] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
NF-kappa B is a key transcription factor that dictates the outcome of diverse immune responses. How NF-kappa B is regulated by multiple activating receptors that are engaged during natural killer (NK)-target cell contact remains undefined. Here we show that sole engagement of NKG2D, 2B4 or DNAM-1 is insufficient for NF-kappa B activation. Rather, cooperation between these receptors is required at the level of Vav1 for synergistic NF-kappa B activation. Vav1-dependent synergistic signalling requires a separate PI3K-Akt signal, primarily mediated by NKG2D or DNAM-1, for optimal p65 phosphorylation and NF-kappa B activation. Vav1 controls downstream p65 phosphorylation and NF-kappa B activation. Synergistic signalling is defective in X-linked lymphoproliferative disease (XLP1) NK cells entailing 2B4 dysfunction and required for p65 phosphorylation by PI3K-Akt signal, suggesting stepwise signalling checkpoint for NF-kappa B activation. Thus, our study provides a framework explaining how signals from different activating receptors are coordinated to determine specificity and magnitude of NF-kappa B activation and NK cell responses.
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