PMID- 21768114
OWN - NLM
STAT- MEDLINE
DCOM- 20111205
LR  - 20211020
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 286
IP  - 36
DP  - 2011 Sep 9
TI  - Cooperative regulation of NOTCH1 protein-phosphatidylinositol 3-kinase (PI3K) 
      signaling by NOD1, NOD2, and TLR2 receptors renders enhanced refractoriness to 
      transforming growth factor-beta (TGF-beta)- or cytotoxic T-lymphocyte antigen 4 
      (CTLA-4)-mediated impairment of human dendritic cell maturation.
PG  - 31347-60
LID - 10.1074/jbc.M111.232413 [doi]
AB  - Dendritic cells (DCs) as sentinels of the immune system are important for 
      eliciting both primary and secondary immune responses to a plethora of microbial 
      pathogens. Cooperative stimulation of a complex set of pattern-recognition 
      receptors, including TLR2 and nucleotide-binding oligomerization domain 
      (NOD)-like receptors on DCs, acts as a rate-limiting factor in determining the 
      initiation and mounting of the robust immune response. It underscores the need 
      for "decoding" these multiple receptor interactions. In this study, we 
      demonstrate that TLR2 and NOD receptors cooperatively regulate functional 
      maturation of human DCs. Intriguingly, synergistic stimulation of TLR2 and NOD 
      receptors renders enhanced refractoriness to TGF-beta- or CTLA-4-mediated impairment 
      of human DC maturation. Signaling perturbation data suggest that NOTCH1-PI3K 
      signaling dynamics assume critical importance in TLR2- and NOD receptor-mediated 
      surmounting of CTLA-4- and TGF-beta-suppressed maturation of human DCs. 
      Interestingly, the NOTCH1-PI3K signaling axis holds the capacity to regulate DC 
      functions by virtue of PKCdelta-MAPK-dependent activation of NF-kappaB. This study 
      provides mechanistic and functional insights into TLR2- and NOD receptor-mediated 
      regulation of DC functions and unravels NOTCH1-PI3K as a signaling cohort for 
      TLR2 and NOD receptors. These findings serve in building a conceptual foundation 
      for the design of improved strategies for adjuvants and immunotherapies against 
      infectious diseases.
FAU - Ghorpade, Devram Sampat
AU  - Ghorpade DS
AD  - Department of Microbiology and Cell Biology, Indian Institute of Science, 
      Bangalore 560012, India.
FAU - Kaveri, Srini V
AU  - Kaveri SV
FAU - Bayry, Jagadeesh
AU  - Bayry J
FAU - Balaji, Kithiganahalli Narayanaswamy
AU  - Balaji KN
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Retracted Publication
DEP - 20110715
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (CTLA-4 Antigen)
RN  - 0 (CTLA4 protein, human)
RN  - 0 (NF-kappa B)
RN  - 0 (NOD1 protein, human)
RN  - 0 (NOD2 protein, human)
RN  - 0 (Nod1 Signaling Adaptor Protein)
RN  - 0 (Nod2 Signaling Adaptor Protein)
RN  - 0 (Receptor, Notch1)
RN  - 0 (TLR2 protein, human)
RN  - 0 (Toll-Like Receptor 2)
RN  - 0 (Transforming Growth Factor beta)
RN  - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase)
SB  - IM
RIN - J Biol Chem. 2019 Dec 13;294(50):19449. PMID: 31836676
MH  - CTLA-4 Antigen/immunology
MH  - Cell Differentiation/immunology
MH  - Dendritic Cells/*cytology/immunology
MH  - Humans
MH  - NF-kappa B/metabolism
MH  - Nod1 Signaling Adaptor Protein/immunology/*metabolism
MH  - Nod2 Signaling Adaptor Protein/immunology/*metabolism
MH  - Phosphatidylinositol 3-Kinase/immunology/*metabolism
MH  - Receptor, Notch1/immunology/*metabolism
MH  - Signal Transduction/*immunology
MH  - Toll-Like Receptor 2/immunology/*metabolism
MH  - Transforming Growth Factor beta/immunology
PMC - PMC3173143
EDAT- 2011/07/20 06:00
MHDA- 2011/12/13 00:00
PMCR- 2012/09/09
CRDT- 2011/07/20 06:00
PHST- 2011/07/20 06:00 [entrez]
PHST- 2011/07/20 06:00 [pubmed]
PHST- 2011/12/13 00:00 [medline]
PHST- 2012/09/09 00:00 [pmc-release]
AID - S0021-9258(20)72245-3 [pii]
AID - M111.232413 [pii]
AID - 10.1074/jbc.M111.232413 [doi]
PST - ppublish
SO  - J Biol Chem. 2011 Sep 9;286(36):31347-60. doi: 10.1074/jbc.M111.232413. Epub 2011 
      Jul 15.