DNA-PKcs, but not TLR9, is required for activation of Akt by CpG-DNA Journal Article
| Authors: | Dragoi, A. M.; Fu, X.; Ivanov, S.; Zhang, P.; Sheng, L.; Wu, D.; Li, G. C.; Chu, W. M. |
| Article Title: | DNA-PKcs, but not TLR9, is required for activation of Akt by CpG-DNA |
| Abstract: | 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. © 2005 European Molecular Biology Organization | All Rights Reserved. |
| Keywords: | signal transduction; protein kinase b; controlled study; dna-binding proteins; proto-oncogene proteins; nonhuman; animal cell; mouse; animals; mice; mice, knockout; cell survival; cells, cultured; bone marrow; enzyme activation; in vitro study; phosphorylation; dna; enzyme phosphorylation; cpg island; protein-serine-threonine kinases; recombinant protein; proto-oncogene proteins c-akt; active transport, cell nucleus; akt; macrophages; ex vivo study; dna responsive element; enzyme purification; immunocompetent cell; oligodeoxynucleotide; enzyme active site; receptors, cell surface; toll-like receptor 9; oligodeoxyribonucleotides; toll like receptor 9; dna dependent protein kinase; dna-activated protein kinase; macrophage activation; dna-pkcs; protein serine kinase; tlr9; cpg-dna |
| Journal Title: | EMBO Journal |
| Volume: | 24 |
| Issue: | 4 |
| ISSN: | 0261-4189 |
| Publisher: | Wiley Blackwell |
| Date Published: | 2005-02-23 |
| Start Page: | 779 |
| End Page: | 789 |
| Language: | English |
| DOI: | 10.1038/sj.emboj.7600539 |
| PUBMED: | 15678105 |
| PROVIDER: | scopus |
| PMCID: | PMC549614 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 53" - "Export Date: 24 October 2012" - "CODEN: EMJOD" - "Source: Scopus" |
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