PMID- 10581243
OWN - NLM
STAT- MEDLINE
DCOM- 20000131
LR  - 20171116
IS  - 0261-4189 (Print)
IS  - 0261-4189 (Linking)
VI  - 18
IP  - 23
DP  - 1999 Dec 1
TI  - NF-kappaB activation by a signaling complex containing TRAF2, TANK and TBK1, a
      novel IKK-related kinase.
PG  - 6694-704
AB  - The activation of NF-kappaB by receptors in the tumor necrosis factor (TNF)
      receptor and Toll/interleukin-1 (IL-1) receptor families requires the TRAF family
      of adaptor proteins. Receptor oligomerization causes the recruitment of TRAFs to 
      the receptor complex, followed by the activation of a kinase cascade that results
      in the phosphorylation of IkappaB. TANK is a TRAF-binding protein that can
      inhibit the binding of TRAFs to receptor tails and can also inhibit NF-kappaB
      activation by these receptors. However, TANK also displays the ability to
      stimulate TRAF-mediated NF-kappaB activation. In this report, we investigate the 
      mechanism of the stimulatory activity of TANK. We find that TANK interacts with
      TBK1 (TANK-binding kinase 1), a novel IKK-related kinase that can activate
      NF-kappaB in a kinase-dependent manner. TBK1, TANK and TRAF2 can form a ternary
      complex, and complex formation appears to be required for TBK1 activity.
      Kinase-inactive TBK1 inhibits TANK-mediated NF-kappaB activation but does not
      block the activation mediated by TNF-alpha, IL-1 or CD40. The TBK1-TANK-TRAF2
      signaling complex functions upstream of NIK and the IKK complex and represents an
      alternative to the receptor signaling complex for TRAF-mediated activation of
      NF-kappaB.
FAU - Pomerantz, J L
AU  - Pomerantz JL
AD  - Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
FAU - Baltimore, D
AU  - Baltimore D
LA  - eng
SI  - GENBANK/AF191838
SI  - GENBANK/AF191839
GR  - AI42549-02/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
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 (CD40 Antigens)
RN  - 0 (Interleukin-1)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (NF-kappa B)
RN  - 0 (Proteins)
RN  - 0 (TANK protein, human)
RN  - 0 (TNF Receptor-Associated Factor 2)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 147205-72-9 (CD40 Ligand)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (TBK1 protein, human)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
SB  - S
MH  - *Adaptor Proteins, Signal Transducing
MH  - Amino Acid Sequence
MH  - CD40 Antigens/metabolism
MH  - CD40 Ligand
MH  - Cell Line
MH  - Dose-Response Relationship, Drug
MH  - *Enzyme Activation
MH  - Humans
MH  - Interleukin-1/metabolism
MH  - JNK Mitogen-Activated Protein Kinases
MH  - Membrane Glycoproteins/metabolism
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Molecular Sequence Data
MH  - NF-kappa B/*metabolism
MH  - Protein-Serine-Threonine Kinases/*metabolism
MH  - Proteins/*metabolism
MH  - Sequence Homology, Amino Acid
MH  - *Signal Transduction
MH  - TNF Receptor-Associated Factor 2
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Two-Hybrid System Techniques
PMC - PMC1171732
EDAT- 1999/12/03 00:00
MHDA- 1999/12/03 00:01
CRDT- 1999/12/03 00:00
PHST- 1999/12/03 00:00 [pubmed]
PHST- 1999/12/03 00:01 [medline]
PHST- 1999/12/03 00:00 [entrez]
AID - 10.1093/emboj/18.23.6694 [doi]
PST - ppublish
SO  - EMBO J. 1999 Dec 1;18(23):6694-704. doi: 10.1093/emboj/18.23.6694.