PMID- 12591926
OWN - NLM
STAT- MEDLINE
DCOM- 20030716
LR  - 20220408
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 278
IP  - 17
DP  - 2003 Apr 25
TI  - Tumor necrosis factor (TNF)-induced germinal center kinase-related (GCKR) and 
      stress-activated protein kinase (SAPK) activation depends upon the E2/E3 complex 
      Ubc13-Uev1A/TNF receptor-associated factor 2 (TRAF2).
PG  - 15429-34
AB  - Tumor necrosis factor (TNF)-induced activation of apoptosis signal-regulating 
      kinase 1 (ASK1) and germinal center kinases (GCKs) and the subsequent activation 
      of stress-activated protein kinases (SAPKs and c-Jun NH(2)-terminal kinases) 
      requires TNF receptor-associated factor 2 (TRAF2). Although the TRAF2 TRAF domain 
      binds ASK1, GCK, and the highly related kinase GCKR, the RING finger domain is 
      needed for their activation. Here, we report that TNF activates GCKR and the SAPK 
      pathway in a manner that depends upon TRAF2 and Ubc13, a member along with Uev1A 
      of a dimeric ubiquitin-conjugating enzyme complex. Interference with Ubc13 
      function or expression inhibits both TNF- and TRAF2-mediated GCKR and SAPK 
      activation, but has a minimal effect on ASK1 activation. TNF signaling leads to 
      TRAF2 polyubiquitination and oligomerization and to the oligomerization, 
      ubiquitination, and activation of GCKR, all of which are sensitive to the 
      disruption of Ubc13 function. These results indicate that the assembly of a TRAF2 
      lysine 63-linked polyubiquitin chain by Ubc13/Uev1A is required for TNF-mediated 
      GCKR and SAPK activation, but may not be required for ASK1 activation.
FAU - Shi, Chong-Shan
AU  - Shi CS
AD  - B Cell Molecular Immunology Section, Laboratory of Immunoregulation, NIAID, 
      National Institutes of Health, Bethesda, Maryland 20892, USA.
FAU - Kehrl, John H
AU  - Kehrl JH
LA  - eng
PT  - Journal Article
DEP - 20030218
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Proteins)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (TNF Receptor-Associated Factor 2)
RN  - 0 (Transcription Factors)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Ubiquitin)
RN  - EC 2.3.2.23 (UBE2V1 protein, human)
RN  - EC 2.3.2.23 (Ubiquitin-Conjugating Enzymes)
RN  - EC 2.7.1.- (MAP4K5 protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 8)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.25 (MAP Kinase Kinase Kinase 5)
RN  - EC 2.7.11.25 (MAP Kinase Kinase Kinases)
RN  - EC 2.7.11.25 (MAP3K5 protein, human)
RN  - EC 6.- (Ligases)
SB  - IM
MH  - Enzyme Activation/drug effects
MH  - Humans
MH  - Ligases/*physiology
MH  - MAP Kinase Kinase Kinase 5
MH  - MAP Kinase Kinase Kinases/metabolism
MH  - Mitogen-Activated Protein Kinase 8
MH  - Mitogen-Activated Protein Kinases/*metabolism
MH  - Protein Serine-Threonine Kinases/*metabolism
MH  - Proteins/*physiology
MH  - Receptors, Tumor Necrosis Factor
MH  - Signal Transduction
MH  - TNF Receptor-Associated Factor 2
MH  - *Transcription Factors
MH  - Tumor Cells, Cultured
MH  - Tumor Necrosis Factor-alpha/*pharmacology
MH  - Ubiquitin/metabolism
MH  - Ubiquitin-Conjugating Enzymes
EDAT- 2003/02/20 04:00
MHDA- 2003/07/17 05:00
CRDT- 2003/02/20 04:00
PHST- 2003/02/20 04:00 [pubmed]
PHST- 2003/07/17 05:00 [medline]
PHST- 2003/02/20 04:00 [entrez]
AID - S0021-9258(19)30354-0 [pii]
AID - 10.1074/jbc.M211796200 [doi]
PST - ppublish
SO  - J Biol Chem. 2003 Apr 25;278(17):15429-34. doi: 10.1074/jbc.M211796200. Epub 2003 
      Feb 18.