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| Subject Categories: Signal Transduction | Immunology |
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| The EMBO Journal
(2005) 24, 779–789, doi:10.1038/sj.emboj.7600539 Published online 27 January 2005 |
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| DNA-PKcs, but not TLR9, is required for activation of Akt by CpG-DNA |
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| Ana-Maria Dragoi1, Xiaoying Fu1, 4, Stanimir Ivanov1, 4, Ping Zhang1, Linbo Sheng2, Dianqing Wu3, Gloria C Li2 and Wen-Ming Chu1 |
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1 Department of Molecular Microbiology and Immunology, Brown University, Providence, RI, USA 2 Departments of Radiation Oncology and Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA 3 Departments of Genetics and Development Biology, University of Connecticut, Health Center, Farmington, CT, USA To whom correspondence should be addressed Wen-Ming Chu, Department of Molecular Microbiology and Immunology, Brown University, Box G-B6, Providence, RI 02912, USA. Tel.: +1 401 863 9786; Fax: +1 401 863 1971; E-mail: wen-ming_chu@brown.edu 4 These authors contributed equally to this work Received 2 June 2004; Accepted 2 December 2004; Published online 27 January 2005. |
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| Abstract |
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| CpG-DNA and its related synthetic CpG oligodeoxynucleotides (CpG-ODNs) play an important role in immune cell survival. It has been suggested that Akt is one of the CpG-DNA-responsive serine/threonine kinases; however, the target protein of CpG-DNA that leads to Akt activation has not been elucidated. Here, we report that ex vivo stimulation of bone marrow-derived macrophages (BMDMs) from mice lacking the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) results in defective phosphorylation and activation of Akt by CpG-DNA. Unexpectedly, loss of the Toll-like receptor 9 has a minimal effect on Akt activation in response to CpG-DNA. Further in vitro analysis using purified DNA-PK and recombinant Akt proteins reveals that DNA-PK directly induces phosphorylation and activation of Akt. In addition, in BMDMs, DNA-PKcs associates with Akt upon CpG-DNA stimulation and triggers transient nuclear translocation of Akt. Thus, our findings establish a novel role for DNA-PKcs in CpG-DNA signaling and define a CpG-DNA/DNA-PKcs/Akt pathway. |
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| Keywords: Akt, CpG-DNA, DNA-PKcs, TLR9 |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated RESEARCHThe EMBO Journal Article (01 Mar 1999) Oncogene Original Article Oncogene Original Article |
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