PMID- 10880445
OWN - NLM
STAT- MEDLINE
DCOM- 20001005
LR  - 20220330
IS  - 0261-4189 (Print)
IS  - 1460-2075 (Electronic)
IS  - 0261-4189 (Linking)
VI  - 19
IP  - 13
DP  - 2000 Jul 3
TI  - The apoptotic signaling pathway activated by Toll-like receptor-2.
PG  - 3325-36
AB  - The innate immune system uses Toll family receptors to signal for the presence of 
      microbes and initiate host defense. Bacterial lipoproteins (BLPs), which are 
      expressed by all bacteria, are potent activators of Toll-like receptor-2 (TLR2). 
      Here we show that the adaptor molecule, myeloid differentiation factor 88 
      (MyD88), mediates both apoptosis and nuclear factor-kappaB (NF-kappaB) activation 
      by BLP-stimulated TLR2. Inhibition of the NF-kappaB pathway downstream of MyD88 
      potentiates apoptosis, indicating that these two pathways bifurcate at the level 
      of MyD88. TLR2 signals for apoptosis through MyD88 via a pathway involving 
      Fas-associated death domain protein (FADD) and caspase 8. Moreover, MyD88 binds 
      FADD and is sufficient to induce apoptosis. These data indicate that TLR2 is a 
      novel 'death receptor' that engages the apoptotic machinery without a 
      conventional cytoplasmic death domain. Through TLR2, BLP induces the synthesis of 
      the precursor of the pro-inflammatory cytokine interleukin-1beta (IL-1beta). 
      Interestingly, BLP also activates caspase 1 through TLR2, resulting in 
      proteolysis and secretion of mature IL-1beta. These results indicate that caspase 
      activation is an innate immune response to microbial pathogens, culminating in 
      apoptosis and cytokine production.
FAU - Aliprantis, A O
AU  - Aliprantis AO
AD  - Skirball Institute and Department of Microbiology, New York University School of 
      Medicine, 540 First Avenue, New York, NY 1001, USA.
FAU - Yang, R B
AU  - Yang RB
FAU - Weiss, D S
AU  - Weiss DS
FAU - Godowski, P
AU  - Godowski P
FAU - Zychlinsky, A
AU  - Zychlinsky A
LA  - eng
GR  - R01 AI037720/AI/NIAID NIH HHS/United States
GR  - AI 37720-04/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Antigens, Differentiation)
RN  - 0 (Arabidopsis Proteins)
RN  - 0 (Drosophila Proteins)
RN  - 0 (MYD88 protein, human)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (NF-kappa B)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (TLR2 protein, human)
RN  - 0 (Toll-Like Receptor 2)
RN  - 0 (Toll-Like Receptors)
RN  - EC 1.14.19.- (Fatty Acid Desaturases)
RN  - EC 1.14.99.- (Fad7 protein, Arabidopsis)
RN  - EC 3.4.22.- (CASP8 protein, human)
RN  - EC 3.4.22.- (CASP9 protein, human)
RN  - EC 3.4.22.- (Caspase 8)
RN  - EC 3.4.22.- (Caspase 9)
RN  - EC 3.4.22.- (Caspases)
RN  - EC 3.4.22.36 (Caspase 1)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Antigens, Differentiation/metabolism/physiology
MH  - Apoptosis/*physiology
MH  - *Arabidopsis Proteins
MH  - Caspase 1/metabolism
MH  - Caspase 8
MH  - Caspase 9
MH  - Caspases/metabolism
MH  - Cell Line
MH  - *Drosophila Proteins
MH  - Enzyme Activation
MH  - Fatty Acid Desaturases/metabolism
MH  - Humans
MH  - Membrane Glycoproteins/*physiology
MH  - Myeloid Differentiation Factor 88
MH  - NF-kappa B/metabolism
MH  - Protein Binding
MH  - Receptors, Cell Surface/*physiology
MH  - *Receptors, Immunologic
MH  - Signal Transduction/*physiology
MH  - Toll-Like Receptor 2
MH  - Toll-Like Receptors
PMC - PMC313930
EDAT- 2000/07/06 11:00
MHDA- 2000/10/07 11:01
PMCR- 2001/07/03
CRDT- 2000/07/06 11:00
PHST- 2000/07/06 11:00 [pubmed]
PHST- 2000/10/07 11:01 [medline]
PHST- 2000/07/06 11:00 [entrez]
PHST- 2001/07/03 00:00 [pmc-release]
AID - cdd309 [pii]
AID - 10.1093/emboj/19.13.3325 [doi]
PST - ppublish
SO  - EMBO J. 2000 Jul 3;19(13):3325-36. doi: 10.1093/emboj/19.13.3325.