PMID- 15678105
OWN - NLM
STAT- MEDLINE
DCOM- 20050418
LR  - 20211203
IS  - 0261-4189 (Print)
IS  - 1460-2075 (Electronic)
IS  - 0261-4189 (Linking)
VI  - 24
IP  - 4
DP  - 2005 Feb 23
TI  - DNA-PKcs, but not TLR9, is required for activation of Akt by CpG-DNA.
PG  - 779-89
AB  - 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.
FAU - Dragoi, Ana-Maria
AU  - Dragoi AM
AD  - Department of Molecular Microbiology and Immunology, Brown University, 
      Providence, RI 02912, USA.
FAU - Fu, Xiaoying
AU  - Fu X
FAU - Ivanov, Stanimir
AU  - Ivanov S
FAU - Zhang, Ping
AU  - Zhang P
FAU - Sheng, Linbo
AU  - Sheng L
FAU - Wu, Dianqing
AU  - Wu D
FAU - Li, Gloria C
AU  - Li GC
FAU - Chu, Wen-Ming
AU  - Chu WM
LA  - eng
GR  - R01 AI054128/AI/NIAID NIH HHS/United States
GR  - R01 AI054128-01/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20050127
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (CPG-oligonucleotide)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Oligodeoxyribonucleotides)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Tlr9 protein, mouse)
RN  - 0 (Toll-Like Receptor 9)
RN  - EC 2.7.11.1 (DNA-Activated Protein Kinase)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Active Transport, Cell Nucleus/drug effects
MH  - Animals
MH  - Bone Marrow/drug effects/enzymology
MH  - Cells, Cultured
MH  - DNA-Activated Protein Kinase
MH  - DNA-Binding Proteins/*metabolism
MH  - Enzyme Activation
MH  - Macrophages/drug effects/enzymology
MH  - Mice
MH  - Mice, Knockout
MH  - Oligodeoxyribonucleotides/*pharmacology
MH  - Phosphorylation
MH  - Protein Serine-Threonine Kinases/*metabolism
MH  - Proto-Oncogene Proteins/*metabolism
MH  - Proto-Oncogene Proteins c-akt
MH  - Receptors, Cell Surface/metabolism
MH  - Toll-Like Receptor 9
PMC - PMC549614
EDAT- 2005/01/29 09:00
MHDA- 2005/04/19 09:00
PMCR- 2005/02/23
CRDT- 2005/01/29 09:00
PHST- 2004/06/02 00:00 [received]
PHST- 2004/12/02 00:00 [accepted]
PHST- 2005/01/29 09:00 [pubmed]
PHST- 2005/04/19 09:00 [medline]
PHST- 2005/01/29 09:00 [entrez]
PHST- 2005/02/23 00:00 [pmc-release]
AID - 7600539 [pii]
AID - 10.1038/sj.emboj.7600539 [doi]
PST - ppublish
SO  - EMBO J. 2005 Feb 23;24(4):779-89. doi: 10.1038/sj.emboj.7600539. Epub 2005 Jan 
      27.